A comprehensive overview of liquid biopsy applications in pediatric solid tumors.

Tomasetti, C., Li, L. & Vogelstein, B. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science 355, 1330–1334 (2017).

pubmed: 28336671 pmcid: 5852673 doi: 10.1126/science.aaf9011

WHO Classification of Tumours Editorial Board. Paediatric Tumours. Lyon (France): International Agency for Research on Cancer, 5th edn, Vol. 7 WHO classification of tumours series. https://publications.iarc.fr/608 (WHO, 2022).

Weiser, D. A. et al. Progress toward liquid biopsies in pediatric solid tumors. Cancer Metastasis Rev. 38, 553–571 (2019).

pubmed: 31836951 pmcid: 6995761 doi: 10.1007/s10555-019-09825-1

Doculara, L., Trahair, T. N., Bayat, N. & Lock, R. B. Circulating tumor DNA in pediatric cancer. Front Mol. Biosci. 9, 885597 (2022).

pubmed: 35647029 pmcid: 9133724 doi: 10.3389/fmolb.2022.885597

Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin. 73, 17–48 (2023).

pubmed: 36633525 doi: 10.3322/caac.21763

Kattner, P. et al. Compare and contrast: pediatric cancer versus adult malignancies. Cancer Metastasis Rev. 38, 673–682 (2019).

pubmed: 31832830 doi: 10.1007/s10555-019-09836-y

Grossi, M. Management and long-term complications of pediatric cancer. Pediatr. Clin. North Am. 45, 1637–1658 (1998).

pubmed: 9889769 doi: 10.1016/S0031-3955(05)70106-1

Sundby, R. T., Pan, A. & Shern, J. F. Liquid biopsies in pediatric oncology: opportunities and obstacles. Curr. Opin. Pediatr. 34, 39–47 (2022).

pubmed: 34840249 doi: 10.1097/MOP.0000000000001088

Christodoulou, E. et al. Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors. NPJ Precis. Oncol. 7, 21 (2023).

pubmed: 36805676 pmcid: 9941464 doi: 10.1038/s41698-023-00357-0

Sweet-Cordero, E. A. & Biegel, J. A. The genomic landscape of pediatric cancers: Implications for diagnosis and treatment. Science 363, 1170–1175 (2019).

pubmed: 30872516 pmcid: 7757338 doi: 10.1126/science.aaw3535

Grobner, S. N. et al. The landscape of genomic alterations across childhood cancers. Nature 555, 321–327 (2018).

pubmed: 29489754 doi: 10.1038/nature25480

Parsa, N. Environmental factors inducing human cancers. Iran. J. Public Health 41, 1–9 (2012).

pubmed: 23304670 pmcid: 3521879

Wu, S., Zhu, W., Thompson, P. & Hannun, Y. A. Evaluating intrinsic and non-intrinsic cancer risk factors. Nat. Commun. 9, 3490 (2018).

pubmed: 30154431 pmcid: 6113228 doi: 10.1038/s41467-018-05467-z

Doll, R. & Peto, R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66, 1191–1308 (1981).

pubmed: 7017215 doi: 10.1093/jnci/66.6.1192

Zhang, J. et al. Germline mutations in predisposition genes in pediatric cancer. N. Engl. J. Med. 373, 2336–2346 (2015).

pubmed: 26580448 pmcid: 4734119 doi: 10.1056/NEJMoa1508054

Bakhuizen, J. J. et al. Assessment of cancer predisposition syndromes in a national cohort of children with a neoplasm. JAMA Netw. Open 6, e2254157 (2023).

pubmed: 36735256 pmcid: 9898819 doi: 10.1001/jamanetworkopen.2022.54157

Miller, K. D. et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J. Clin. 69, 363–385 (2019).

pubmed: 31184787 doi: 10.3322/caac.21565

Bryant, R. Managing side effects of childhood cancer treatment. J. Pediatr. Nurs. 18, 113–125 (2003).

pubmed: 12720208 doi: 10.1053/jpdn.2003.11

Basak, D., Arrighi, S., Darwiche, Y. & Deb, S. Comparison of anticancer drug toxicities: paradigm shift in adverse effect profile. Life (Basel) 12, 48 (2021).

pubmed: 35054441

Lone, S. N. et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments. Mol. Cancer 21, 79 (2022).

pubmed: 35303879 pmcid: 8932066 doi: 10.1186/s12943-022-01543-7

Weiser, D. A., Kaste, S. C., Siegel, M. J. & Adamson, P. C. Imaging in childhood cancer: a Society for Pediatric Radiology and Children’s Oncology Group Joint Task Force report. Pediatr. Blood Cancer 60, 1253–1260 (2013).

pubmed: 23572212 pmcid: 4636336 doi: 10.1002/pbc.24533

Stankunaite, R. et al. Liquid biopsy for children with central nervous system tumours: clinical integration and technical considerations. Front Pediatr. 10, 957944 (2022).

pubmed: 36467471 pmcid: 9709284 doi: 10.3389/fped.2022.957944

Anderson, N. M. & Simon, M. C. The tumor microenvironment. Curr. Biol. 30, R921–R925 (2020).

pubmed: 32810447 pmcid: 8194051 doi: 10.1016/j.cub.2020.06.081

Kahana-Edwin, S., Cain, L. E. & Karpelowsky, J. Roadmap to liquid biopsy biobanking from pediatric cancers-challenges and opportunities. Biopreserv. Biobank 19, 124–129 (2021).

pubmed: 33493007 doi: 10.1089/bio.2020.0117

Madlener, S. & Gojo, J. Liquid biomarkers for pediatric brain tumors: biological features, advantages and perspectives. J. Pers. Med. 10, 254 (2020).

pubmed: 33260839 pmcid: 7711550 doi: 10.3390/jpm10040254

Werner, B., Warton, K. & Ford, C. E. Transcending blood-opportunities for alternate liquid biopsies in oncology. Cancers (Basel) 14, 1309 (2022).

pubmed: 35267615 doi: 10.3390/cancers14051309

Peng, M., Chen, C., Hulbert, A., Brock, M. V. & Yu, F. Non-blood circulating tumor DNA detection in cancer. Oncotarget 8, 69162–69173 (2017).

pubmed: 28978187 pmcid: 5620327 doi: 10.18632/oncotarget.19942

McEwen, A. E., Leary, S. E. S. & Lockwood, C. M. Beyond the blood: CSF-derived cfDNA for diagnosis and characterization of CNS tumors. Front Cell Dev. Biol. 8, 45 (2020).

pubmed: 32133357 pmcid: 7039816 doi: 10.3389/fcell.2020.00045

Miller, A. M. & Karajannis, M. A. Current role and future potential of CSF ctDNA for the diagnosis and clinical management of pediatric central nervous system tumors. J. Natl. Compr. Canc. Netw. 20, 1363–1369 (2022).

pubmed: 36509077 pmcid: 10050207

Liu, A. P., Northcott, P. A., Robinson, G. W. & Gajjar, A. Circulating tumor DNA profiling for childhood brain tumors: technical challenges and evidence for utility. Lab Invest. 102, 134–142 (2022).

pubmed: 34934181 doi: 10.1038/s41374-021-00719-x

Andersson, D., Fagman, H., Dalin, M. G. & Stahlberg, A. Circulating cell-free tumor DNA analysis in pediatric cancers. Mol. Asp. Med. 72, 100819 (2020).

doi: 10.1016/j.mam.2019.09.003

Nikanjam, M., Kato, S. & Kurzrock, R. Liquid biopsy: current technology and clinical applications. J. Hematol. Oncol. 15, 131 (2022).

pubmed: 36096847 pmcid: 9465933 doi: 10.1186/s13045-022-01351-y

Alix-Panabieres, C. & Pantel, K. Liquid biopsy: from discovery to clinical application. Cancer Discov. 11, 858–873 (2021).

pubmed: 33811121 doi: 10.1158/2159-8290.CD-20-1311

Liu, F., Xiong, Q. W., Wang, J. H. & Peng, W. X. Roles of lncRNAs in childhood cancer: current landscape and future perspectives. Front Oncol. 13, 1060107 (2023).

pubmed: 36923440 pmcid: 10008945 doi: 10.3389/fonc.2023.1060107

Varkey, J. & Nicolaides, T. Tumor-educated platelets: a review of current and potential applications in solid tumors. Cureus 13, e19189 (2021).

pubmed: 34873529 pmcid: 8635758

Narayan, P. et al. State of the science and future directions for liquid biopsies in drug development. Oncologist 25, 730–732 (2020).

pubmed: 32510742 pmcid: 7485357 doi: 10.1634/theoncologist.2020-0246

Sato, Y. Clinical utility of liquid biopsy-based companion diagnostics in the non-small-cell lung cancer treatment. Explor. Target Antitumor Ther. 3, 630–642 (2022).

pubmed: 36338524 pmcid: 9630093 doi: 10.37349/etat.2022.00104

Cisneros-Villanueva, M. et al. Cell-free DNA analysis in current cancer clinical trials: a review. Br. J. Cancer 126, 391–400 (2022).

pubmed: 35027672 pmcid: 8810765 doi: 10.1038/s41416-021-01696-0

Ignatiadis, M., Sledge, G. W. & Jeffrey, S. S. Liquid biopsy enters the clinic—implementation issues and future challenges. Nat. Rev. Clin. Oncol. 18, 297–312 (2021).

pubmed: 33473219 doi: 10.1038/s41571-020-00457-x

Alexandrou, G. et al. The evolution of affordable technologies in liquid biopsy diagnostics: the key to clinical implementation. Cancers (Basel) 15, 5434 (2023).

pubmed: 38001698 doi: 10.3390/cancers15225434

Archer™ LIQUIDPlex™ Universal Solid Tumor panel, https://www.idtdna.com/pages/products/next-generation-sequencing/archer-ngs-assay-solutions/solid-tumor-research/archer-liquidplex-universal-panel (2024).

Yang, R., Zheng, S. & Dong, R. Circulating tumor cells in neuroblastoma: current status and future perspectives. Cancer Med. 12, 7–19 (2023).

pubmed: 35632981 doi: 10.1002/cam4.4893

Wei, M., Ye, M., Dong, K. & Dong, R. Circulating tumor DNA in neuroblastoma. Pediatr. Blood Cancer 67, e28311 (2020).

pubmed: 32729220 doi: 10.1002/pbc.28311

Kaatsch, P. Epidemiology of childhood cancer. Cancer Treat. Rev. 36, 277–285 (2010).

pubmed: 20231056 doi: 10.1016/j.ctrv.2010.02.003

Mahapatra, S., Challagundla, K. B. Neuroblastoma. [Updated 2023 Jul 10]. In StatPearls [Internet]. Treasure Island (FL) (StatPearls Publishing 2024). Available from: https://www.ncbi.nlm.nih.gov/books/NBK448111/

Krystal, J. & Foster, J. H. Treatment of high-risk neuroblastoma. Children (Basel) 10, 1302 (2023).

Trigg, R. M., Shaw, J. A. & Turner, S. D. Opportunities and challenges of circulating biomarkers in neuroblastoma. Open Biol. 9, 190056 (2019).

pubmed: 31088252 pmcid: 6544987 doi: 10.1098/rsob.190056

Cohn, S. L. et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J. Clin. Oncol. 27, 289–297 (2009).

pubmed: 19047291 pmcid: 2650388 doi: 10.1200/JCO.2008.16.6785

Matthay, K. K. et al. Neuroblastoma. Nat. Rev. Dis. Prim. 2, 16078 (2016).

pubmed: 27830764 doi: 10.1038/nrdp.2016.78

Lerone, M. et al. Molecular genetics in neuroblastoma prognosis. Children (Basel) 8, 456 (2021).

Ma, J. et al. Exosomal hsa-miR199a-3p promotes proliferation and migration in neuroblastoma. Front Oncol. 9, 459 (2019).

pubmed: 31249805 pmcid: 6582313 doi: 10.3389/fonc.2019.00459

Lak, N. S. M. et al. Cell-free RNA from plasma in patients with neuroblastoma: exploring the technical and clinical potential. Cancers (Basel) 15, 2108 (2023).

Abbasi, M. R. et al. Bone marrows from neuroblastoma patients: an excellent source for tumor genome analyses. Mol. Oncol. 9, 545–554 (2015).

pubmed: 25467309 doi: 10.1016/j.molonc.2014.10.010

Batth, I. S. et al. Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients. Int. J. Cancer 147, 3550–3559 (2020).

pubmed: 32506485 pmcid: 7839076 doi: 10.1002/ijc.33140

Burchill, S. A. et al. Circulating neuroblastoma cells detected by reverse transcriptase polymerase chain reaction for tyrosine hydroxylase mRNA are an independent poor prognostic indicator in stage 4 neuroblastoma in children over 1 year. J. Clin. Oncol. 19, 1795–1801 (2001).

pubmed: 11251011 doi: 10.1200/JCO.2001.19.6.1795

Liu, X. et al. Circulating tumor cells detection in neuroblastoma patients by EpCAM-independent enrichment and immunostaining-fluorescence in situ hybridization. EBioMedicine 35, 244–250 (2018).

pubmed: 30104180 pmcid: 6154868 doi: 10.1016/j.ebiom.2018.08.005

Kuroda, T., Saeki, M., Nakano, M. & Mizutani, S. Clinical application of minimal residual neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction. J. Pediatr. Surg. 32, 69–72 (1997).

pubmed: 9021573 doi: 10.1016/S0022-3468(97)90097-X

Lee, N. H. et al. Clinical significance of tyrosine hydroxylase mRNA transcripts in peripheral blood at diagnosis in patients with neuroblastoma. Cancer Res. Treat. 48, 1399–1407 (2016).

pubmed: 27034145 pmcid: 5080821 doi: 10.4143/crt.2015.481

Moss, T. J. et al. Clonogenicity of circulating neuroblastoma cells: implications regarding peripheral blood stem cell transplantation. Blood 83, 3085–3089 (1994).

pubmed: 7910052 doi: 10.1182/blood.V83.10.3085.3085

Merugu, S. et al. Detection of circulating and disseminated neuroblastoma cells using the imagestream flow cytometer for use as predictive and pharmacodynamic biomarkers. Clin. Cancer Res. 26, 122–134 (2020).

pubmed: 31767563 doi: 10.1158/1078-0432.CCR-19-0656

Moss, T. J. & Sanders, D. G. Detection of neuroblastoma cells in blood. J. Clin. Oncol. 8, 736–740 (1990).

pubmed: 2179482 doi: 10.1200/JCO.1990.8.4.736

Gao, Y., Li, G., Zhang, X., Xu, Q. & Zheng, B. Detection of neuroblastoma cells in blood by reverse transcriptase-polymerase chain reaction. Chin. Med. J. (Engl.) 110, 341–345 (1997).

pubmed: 9594298

Miyajima, Y., Kato, K., Numata, S., Kudo, K. & Horibe, K. Detection of neuroblastoma cells in bone marrow and peripheral blood at diagnosis by the reverse transcriptase-polymerase chain reaction for tyrosine hydroxylase mRNA. Cancer 75, 2757–2761 (1995).

pubmed: 7743482 doi: 10.1002/1097-0142(19950601)75:11<2757::AID-CNCR2820751120>3.0.CO;2-S

Corrias, M. V. et al. Detection of neuroblastoma cells in bone marrow and peripheral blood by different techniques: accuracy and relationship with clinical features of patients. Clin. Cancer Res. 10, 7978–7985 (2004).

pubmed: 15585633 doi: 10.1158/1078-0432.CCR-04-0815

Yanagisawa, T. Y. et al. Detection of the PGP9.5 and tyrosine hydroxylase mRNAs for minimal residual neuroblastoma cells in bone marrow and peripheral blood. Tohoku J. Exp. Med. 184, 229–240 (1998).

pubmed: 9591338 doi: 10.1620/tjem.184.229

Pagani, A. et al. Detection procedures for neuroblastoma cells metastatic to blood and bone marrow: blinded comparison of chromogranin A heminested reverse transcription polymerase chain reaction to tyrosine hydroxylase nested reverse transcription polymerase chain reaction and to anti-GD2 immunocytology. Diagn. Mol. Pathol. 11, 98–106 (2002).

pubmed: 12045713 doi: 10.1097/00019606-200206000-00006

Oltra, S. et al. The doublecortin gene, a new molecular marker to detect minimal residual disease in neuroblastoma. Diagn. Mol. Pathol. 14, 53–57 (2005).

pubmed: 15714065 doi: 10.1097/01.pas.0000149876.32376.c0

Burchill, S. A., Bradbury, F. M., Selby, P. & Lewis, I. J. Early clinical evaluation of neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosine hydroxylase mRNA. Eur. J. Cancer 31a, 553–556 (1995).

pubmed: 7576966 doi: 10.1016/0959-8049(95)00053-L

Hirase, S. et al. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients. Oncol. Lett. 12, 1119–1123 (2016).

pubmed: 27446404 pmcid: 4950657 doi: 10.3892/ol.2016.4682

Corrias, M. V. et al. Event-free survival of infants and toddlers enrolled in the HR-NBL-1/SIOPEN trial is associated with the level of neuroblastoma mRNAs at diagnosis. Pediatr. Blood Cancer 65, e27052 (2018).

pubmed: 29603574 doi: 10.1002/pbc.27052

Cheung, I. Y., Feng, Y., Gerald, W. & Cheung, N. K. Exploiting gene expression profiling to identify novel minimal residual disease markers of neuroblastoma. Clin. Cancer Res. 14, 7020–7027 (2008).

pubmed: 18980998 pmcid: 2670609 doi: 10.1158/1078-0432.CCR-08-0541

Marachelian, A. et al. Expression of five neuroblastoma genes in bone marrow or blood of patients with relapsed/refractory neuroblastoma provides a new biomarker for disease and prognosis. Clin. Cancer Res. 23, 5374–5383 (2017).

pubmed: 28559462 doi: 10.1158/1078-0432.CCR-16-2647

Faulkner, L. B. et al. High-sensitivity immunocytologic analysis of neuroblastoma cells in paired blood and marrow samples. J. Hematother. 7, 361–366 (1998).

pubmed: 9735867 doi: 10.1089/scd.1.1998.7.361

Burchill, S. A., Lewis, I. J. & Selby, P. Improved methods using the reverse transcriptase polymerase chain reaction to detect tumour cells. Br. J. Cancer 79, 971–977 (1999).

pubmed: 10070899 pmcid: 2362660 doi: 10.1038/sj.bjc.6690155

Thwin, K. K. M. et al. Level of seven neuroblastoma-associated mRNAs detected by droplet digital PCR is associated with tumor relapse/regrowth of high-risk neuroblastoma patients. J. Mol. Diagn. 22, 236–246 (2020).

pubmed: 31837427 doi: 10.1016/j.jmoldx.2019.10.012

Uemura, S. et al. Limited correlation between tumor markers and minimal residual disease detected by seven neuroblastoma-associated mRNAs in high-risk neuroblastoma patients. Mol. Clin. Oncol. 15, 137 (2021).

pubmed: 34055352 pmcid: 8145602 doi: 10.3892/mco.2021.2299

Cheung, I. Y., Sahota, A. & Cheung, N. K. Measuring circulating neuroblastoma cells by quantitative reverse transcriptase-polymerase chain reaction analysis. Cancer 101, 2303–2308 (2004).

pubmed: 15484213 doi: 10.1002/cncr.20660

Yanez, Y. et al. Minimal disease detection in peripheral blood and bone marrow from patients with non-metastatic neuroblastoma. J. Cancer Res. Clin. Oncol. 137, 1263–1272 (2011).

pubmed: 21706131 doi: 10.1007/s00432-011-0997-x

Oltra, S. et al. Minimal residual disease in neuroblastoma: to GAGE or not to GAGE. Oncol. Res. 14, 291–295 (2004).

pubmed: 15206491 doi: 10.3727/096504003773994824

Bozzi, F. et al. Molecular detection of dopamine decarboxylase expression by means of reverse transcriptase and polymerase chain reaction in bone marrow and peripheral blood: utility as a tumor marker for neuroblastoma. Diagn. Mol. Pathol. 13, 135–143 (2004).

pubmed: 15322424 doi: 10.1097/01.pdm.0000128699.14504.06

Cheung, I. Y. & Cheung, N. K. Molecular detection of GAGE expression in peripheral blood and bone marrow: utility as a tumor marker for neuroblastoma. Clin. Cancer Res. 3, 821–826 (1997).

pubmed: 9815755

Trager, C. et al. mRNAs of tyrosine hydroxylase and dopa decarboxylase but not of GD2 synthase are specific for neuroblastoma minimal disease and predicts outcome for children with high-risk disease when measured at diagnosis. Int. J. Cancer 123, 2849–2855 (2008).

pubmed: 18814238 doi: 10.1002/ijc.23846

Burchill, S. A., Bradbury, F. M., Smith, B., Lewis, I. J. & Selby, P. Neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosine hydroxylase mRNA. Int. J. Cancer 57, 671–675 (1994).

pubmed: 7910809 doi: 10.1002/ijc.2910570510

Lanino, E., Melodia, A., Casalaro, A. & Cornaglia-Ferraris, P. Neuroblastoma cells circulate in peripheral blood. Pediatr. Hematol. Oncol. 6, 193–195 (1989).

pubmed: 2702074 doi: 10.3109/08880018909034286

van Wezel, E. M. et al. Neuroblastoma messenger RNA is frequently detected in bone marrow at diagnosis of localised neuroblastoma patients. Eur. J. Cancer 54, 149–158 (2016).

pubmed: 26796600 doi: 10.1016/j.ejca.2015.11.007

Viprey, V. F. et al. Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study. J. Clin. Oncol. 32, 1074–1083 (2014).

pubmed: 24590653 doi: 10.1200/JCO.2013.53.3604

Swerts, K. et al. Potential application of ELAVL4 real-time quantitative reverse transcription-PCR for detection of disseminated neuroblastoma cells. Clin. Chem. 52, 438–445 (2006).

pubmed: 16384890 doi: 10.1373/clinchem.2005.059485

Parareda, A. et al. Prognostic impact of the detection of microcirculating tumor cells by a real-time RT-PCR assay of tyrosine hydroxylase in patients with advanced neuroblastoma. Oncol. Rep. 14, 1021–1027 (2005).

pubmed: 16142367

Kuroda, T. et al. Prognostic significance of circulating tumor cells and bone marrow micrometastasis in advanced neuroblastoma. J. Pediatr. Surg. 43, 2182–2185 (2008).

pubmed: 19040931 doi: 10.1016/j.jpedsurg.2008.08.046

Träger, C. et al. Quantitative analysis of tyrosine hydroxylase mRNA for sensitive detection of neuroblastoma cells in blood and bone marrow. Clin. Chem. 49, 104–112 (2003).

pubmed: 12507966 doi: 10.1373/49.1.104

Seeger, R. C. et al. Quantitative tumor cell content of bone marrow and blood as a predictor of outcome in stage IV neuroblastoma: a Children’s Cancer Group Study. J. Clin. Oncol. 18, 4067–4076 (2000).

pubmed: 11118468 doi: 10.1200/JCO.2000.18.24.4067

Lambooy, L. H. et al. Real-time analysis of tyrosine hydroxylase gene expression: a sensitive and semiquantitative marker for minimal residual disease detection of neuroblastoma. Clin. Cancer Res. 9, 812–819 (2003).

pubmed: 12576454

Mattano, L. A. Jr., Moss, T. J. & Emerson, S. G. Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction. Cancer Res. 52, 4701–4705 (1992).

pubmed: 1380888

Miyajima, Y. et al. Sequential detection of tumor cells in the peripheral blood and bone marrow of patients with stage IV neuroblastoma by the reverse transcription-polymerase chain reaction for tyrosine hydroxylase mRNA. Cancer 77, 1214–1219 (1996).

pubmed: 8635146 doi: 10.1002/(SICI)1097-0142(19960315)77:6<1214::AID-CNCR31>3.0.CO;2-2

Sanders, D. G., Wiley, F. M. & Moss, T. J. Serial immunocytologic analysis of blood for tumor cells in two patients with neuroblastoma. Cancer 67, 1423–1427 (1991).

pubmed: 1991307 doi: 10.1002/1097-0142(19910301)67:5<1423::AID-CNCR2820670525>3.0.CO;2-L

Tchirkov, A. et al. Significance of molecular quantification of minimal residual disease in metastatic neuroblastoma. J. Hematother. Stem Cell Res 12, 435–442 (2003).

pubmed: 12965080 doi: 10.1089/152581603322286060

Kuroda, T. et al. Surgical treatment of neuroblastoma with micrometastasis. J. Pediatr. Surg. 35, 1638–1642 (2000).

pubmed: 11083442 doi: 10.1053/jpsu.2000.18341

Yanez, Y. et al. TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients. J. Cancer Res. Clin. Oncol. 142, 573–580 (2016).

pubmed: 26498952 doi: 10.1007/s00432-015-2054-7

Kuroda, T. et al. Tumor cell dynamics and metastasis in advanced neuroblastoma. Pediatr. Surg. Int. 21, 859–863 (2005).

pubmed: 16151820 doi: 10.1007/s00383-005-1503-9

Stutterheim, J. et al. Detecting minimal residual disease in neuroblastoma: the superiority of a panel of real-time quantitative PCR markers. Clin. Chem. 55, 1316–1326 (2009).

pubmed: 19460840 doi: 10.1373/clinchem.2008.117945

Hartomo, T. B. et al. Minimal residual disease monitoring in neuroblastoma patients based on the expression of a set of real-time RT-PCR markers in tumor-initiating cells. Oncol. Rep. 29, 1629–1636 (2013).

pubmed: 23417100 doi: 10.3892/or.2013.2286

Corrias, M. V. et al. Multiple target molecular monitoring of bone marrow and peripheral blood samples from patients with localized neuroblastoma and healthy donors. Pediatr. Blood Cancer 58, 43–49 (2012).

pubmed: 21254375 doi: 10.1002/pbc.22960

Viprey, V. F. et al. Standardisation of operating procedures for the detection of minimal disease by QRT-PCR in children with neuroblastoma: quality assurance on behalf of SIOPEN-R-NET. Eur. J. Cancer 43, 341–350 (2007).

pubmed: 17023157 doi: 10.1016/j.ejca.2006.08.007

Kojima, M. et al. Single-cell next-generation sequencing of circulating tumor cells in patients with neuroblastoma. Cancer Sci. 114, 1616–1624 (2023).

pubmed: 36571449 pmcid: 10067419 doi: 10.1111/cas.15707

Stagno, M. J. et al. Epitope detection in monocytes (EDIM) for liquid biopsy including identification of GD2 in childhood neuroblastoma-a pilot study. Br. J. Cancer 127, 1324–1331 (2022).

pubmed: 35864157 pmcid: 9519569 doi: 10.1038/s41416-022-01855-x

Murray, M. J. et al. Solid tumors of childhood display specific serum microRNA profiles. Cancer Epidemiol. Biomark. Prev. 24, 350–360 (2015).

doi: 10.1158/1055-9965.EPI-14-0669

Zeka, F. et al. Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients. JCI Insight 3, 1–13 (2018).

Morini, M. et al. Exosomal microRNAs from longitudinal liquid biopsies for the prediction of response to induction chemotherapy in high-risk neuroblastoma patients: a proof of concept SIOPEN study. Cancers (Basel). 11, 1476 (2019).

Ikematsu, S. et al. Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas. Br. J. Cancer 88, 1522–1526 (2003).

pubmed: 12771916 pmcid: 2377118 doi: 10.1038/sj.bjc.6600938

Cheung, I. Y. & Cheung, N. K. Detection of microscopic disease: comparing histology, immunocytology, and RT-PCR of tyrosine hydroxylase, GAGE, and MAGE. Med. Pediatr. Oncol. 36, 210–212 (2001).

pubmed: 11464887 doi: 10.1002/1096-911X(20010101)36:1<210::AID-MPO1051>3.0.CO;2-F

Cheung, I. Y., Barber, D. & Cheung, N. K. Detection of microscopic neuroblastoma in marrow by histology, immunocytology, and reverse transcription-PCR of multiple molecular markers. Clin. Cancer Res. 4, 2801–2805 (1998).

pubmed: 9829745

Hoon, D. S. et al. Ganglioside GM2/GD2 synthetase mRNA is a marker for detection of infrequent neuroblastoma cells in bone marrow. Am. J. Pathol. 159, 493–500 (2001).

pubmed: 11485908 pmcid: 1850569 doi: 10.1016/S0002-9440(10)61721-X

Stutterheim, J. et al. Methylated RASSF1a is the first specific DNA marker for minimal residual disease testing in neuroblastoma. Clin. Cancer Res 18, 808–814 (2012).

pubmed: 22142825 doi: 10.1158/1078-0432.CCR-11-0849

Vasudevan, S. A. et al. Neuroblastoma-derived secretory protein messenger RNA levels correlate with high-risk neuroblastoma. J. Pediatr. Surg. 42, 148–152 (2007).

pubmed: 17208556 doi: 10.1016/j.jpedsurg.2006.09.064

Cheung, I. Y., Lo Piccolo, M. S., Kushner, B. H., Kramer, K. & Cheung, N. K. Quantitation of GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction: clinical utility in evaluating adjuvant therapy in neuroblastoma. J. Clin. Oncol. 21, 1087–1093 (2003).

pubmed: 12637475 doi: 10.1200/JCO.2003.02.055

Cheung, I. Y., Lo Piccolo, M. S., Collins, N., Kushner, B. H. & Cheung, N. K. Quantitation of GD2 synthase mRNA by real-time reverse transcription-polymerase chain reaction: utility in bone marrow purging of neuroblastoma by anti-GD2 antibody 3F8. Cancer 94, 3042–3048 (2002).

pubmed: 12115395 doi: 10.1002/cncr.10519

Cheung, I. Y. & Cheung, N. K. Quantitation of marrow disease in neuroblastoma by real-time reverse transcription-PCR. Clin. Cancer Res. 7, 1698–1705 (2001).

pubmed: 11410509

Pession, A. et al. Real-time RT-PCR of tyrosine hydroxylase to detect bone marrow involvement in advanced neuroblastoma. Oncol. Rep. 10, 357–362 (2003).

pubmed: 12579272

Cheung, I. Y., Vickers, A. & Cheung, N. K. Sialyltransferase STX (ST8SiaII): a novel molecular marker of metastatic neuroblastoma. Int. J. Cancer 119, 152–156 (2006).

pubmed: 16450393 doi: 10.1002/ijc.21789

van Zogchel, L. M. J. et al. Specific and sensitive detection of neuroblastoma mRNA markers by multiplex RT-qPCR. Cancers (Basel). 13, 150 (2021).

Stutterheim, J. et al. Stability of PCR targets for monitoring minimal residual disease in neuroblastoma. J. Mol. Diagn. 14, 168–175 (2012).

pubmed: 22251610 doi: 10.1016/j.jmoldx.2011.12.002

Gattenloehner, S. et al. A comparison of MyoD1 and fetal acetylcholine receptor expression in childhood tumors and normal tissues: implications for the molecular diagnosis of minimal disease in rhabdomyosarcomas. J. Mol. Diagn. 1, 23–31 (1999).

pubmed: 11272905 pmcid: 1906880 doi: 10.1016/S1525-1578(10)60605-8

Subhash, V. V. et al. Whole-genome sequencing facilitates patient-specific quantitative PCR-based minimal residual disease monitoring in acute lymphoblastic leukaemia, neuroblastoma and Ewing sarcoma. Br. J. Cancer 126, 482–491 (2022).

pubmed: 34471258 doi: 10.1038/s41416-021-01538-z

Zhenjian, Z., Lin, Lei, Miao, Lei, Li, Meng & He, Jing Advances in liquid biopsy in neuroblastoma. Fundam. Res. 2, 903–917 (2022).

doi: 10.1016/j.fmre.2022.08.005

Abbou, S. D., Shulman, D. S., DuBois, S. G. & Crompton, B. D. Assessment of circulating tumor DNA in pediatric solid tumors: the promise of liquid biopsies. Pediatr. Blood Cancer 66, e27595 (2019).

pubmed: 30614191 pmcid: 6550461 doi: 10.1002/pbc.27595

Kojima, M. & Hiyama, E. Circulating tumor cells and tumor progression, metastasis, and poor prognosis in patients with neuroblastoma. Anticancer Res. 43, 4327–4331 (2023).

pubmed: 37772576 doi: 10.21873/anticanres.16627

Trigg, R. M., Turner, S. D., Shaw, J. A. & Jahangiri, L. Diagnostic accuracy of circulating-free DNA for the determination of MYCN amplification status in advanced-stage neuroblastoma: a systematic review and meta-analysis. Br. J. Cancer 122, 1077–1084 (2020).

pubmed: 32015512 pmcid: 7109036 doi: 10.1038/s41416-020-0740-y

Uemura, S. et al. Dynamics of minimal residual disease in neuroblastoma patients. Front Oncol. 9, 455 (2019).

pubmed: 31214500 pmcid: 6558004 doi: 10.3389/fonc.2019.00455

Galardi, A. et al. Exosomal miRNAs in pediatric cancers. Int. J. Mol. Sci. 20, 4600 (2019).

Vellichirammal, N. N., Chaturvedi, N. K., Joshi, S. S., Coulter, D. W. & Guda, C. Fusion genes as biomarkers in pediatric cancers: a review of the current state and applicability in diagnostics and personalized therapy. Cancer Lett. 499, 24–38 (2021).

pubmed: 33248210 doi: 10.1016/j.canlet.2020.11.015

Gholamin, S. et al. GD2-targeted immunotherapy and potential value of circulating microRNAs in neuroblastoma. J. Cell Physiol. 233, 866–879 (2018).

pubmed: 28145567 doi: 10.1002/jcp.25793

Segura, M. F. et al. Methodological advances in the discovery of novel neuroblastoma therapeutics. Expert Opin. Drug Discov. 17, 167–179 (2022).

pubmed: 34807782 doi: 10.1080/17460441.2022.2002297

Andreeva, N., Usman, N. & Druy, A. MicroRNAs as prospective biomarkers, therapeutic targets and pharmaceuticals in neuroblastoma. Mol. Biol. Rep. 50, 1895–1912 (2023).

pubmed: 36520359 doi: 10.1007/s11033-022-08137-y

Galardi, A. et al. MicroRNAs in neuroblastoma: biomarkers with therapeutic potential. Curr. Med Chem. 25, 584–600 (2018).

pubmed: 28971761 doi: 10.2174/0929867324666171003120335

Van Paemel, R. et al. The pitfalls and promise of liquid biopsies for diagnosing and treating solid tumors in children: a review. Eur. J. Pediatr. 179, 191–202 (2020).

pubmed: 31897843 pmcid: 6971142 doi: 10.1007/s00431-019-03545-y

Bhavsar, S. P. Recent advances in the roles of exosomal microRNAs in neuroblastoma. Front Oncol. 12, 1091847 (2022).

pubmed: 36793342 doi: 10.3389/fonc.2023.1091847

de Carvalho, I. N., de Freitas, R. M. & Vargas, F. R. Translating microRNAs into biomarkers: What is new for pediatric cancer? Med. Oncol. 33, 49 (2016).

pubmed: 27085875 doi: 10.1007/s12032-016-0766-4

Bettegowda, C. et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med. 6, 224ra224 (2014).

doi: 10.1126/scitranslmed.3007094

Klega, K. et al. Detection of somatic structural variants enables quantification and characterization of circulating tumor DNA in children with solid tumors. JCO Precis. Oncol. 2018, PO.17.00285 (2018).

pubmed: 30027144

Ruas, J. S. et al. Somatic copy number alteration in circulating tumor DNA for monitoring of pediatric patients with cancer. Biomedicines 11, 1082 (2023).

van Zogchel, L. M. J. et al. Novel circulating hypermethylated RASSF1A ddPCR for liquid biopsies in patients with pediatric solid tumors. JCO Precis. Oncol. 5, PO.21.00130 (2021).

pubmed: 34820594 pmcid: 8608265

Peitz, C. et al. Multiplexed quantification of four neuroblastoma DNA targets in a single droplet digital PCR reaction. J. Mol. Diagn. 22, 1309–1323 (2020).

pubmed: 32858250 doi: 10.1016/j.jmoldx.2020.07.006

Bosse, K. R. & Maris, J. M. Advances in the translational genomics of neuroblastoma: from improving risk stratification and revealing novel biology to identifying actionable genomic alterations. Cancer 122, 20–33 (2016).

pubmed: 26539795 doi: 10.1002/cncr.29706

Shirai, R. et al. Quantitative assessment of copy number alterations by liquid biopsy for neuroblastoma. Genes Chromosomes Cancer 61, 662–669 (2022).

pubmed: 35655408 doi: 10.1002/gcc.23073

Gelineau, N. U. et al. Case series on clinical applications of liquid biopsy in pediatric solid tumors: towards improved diagnostics and disease monitoring. Front Oncol. 13, 1209150 (2023).

pubmed: 37664065 pmcid: 10473251 doi: 10.3389/fonc.2023.1209150

van Zogchel, L. M. J. et al. Targeted locus amplification to develop robust patient-specific assays for liquid biopsies in pediatric solid tumors. Front Oncol. 13, 1124737 (2023).

pubmed: 37152023 pmcid: 10157037 doi: 10.3389/fonc.2023.1124737

Lopez-Carrasco, A. et al. Intra-tumour genetic heterogeneity and prognosis in high-risk neuroblastoma. Cancers (Basel) 13, 5173 (2021).

pubmed: 34680323 doi: 10.3390/cancers13205173

Van Paemel, R. et al. The feasibility of using liquid biopsies as a complementary assay for copy number aberration profiling in routinely collected paediatric cancer patient samples. Eur. J. Cancer 160, 12–23 (2022).

pubmed: 34794856 doi: 10.1016/j.ejca.2021.09.022

Cahn, F. et al. Blood-derived liquid biopsies using foundation One((R)) liquid CDx for children and adolescents with high-risk malignancies: a monocentric experience. Cancers (Basel) 14, 2774 (2022).

pubmed: 35681754 doi: 10.3390/cancers14112774

Michalowski, M. B. et al. Methylation of tumor-suppressor genes in neuroblastoma: The RASSF1A gene is almost always methylated in primary tumors. Pediatr. Blood Cancer 50, 29–32 (2008).

pubmed: 17570703 doi: 10.1002/pbc.21279

Vaisvila, R. et al. Enzymatic methyl sequencing detects DNA methylation at single-base resolution from picograms of DNA. Genome Res. 31, 1280–1289 (2021).

pubmed: 34140313 pmcid: 8256858 doi: 10.1101/gr.266551.120

Trinidad, E. M. et al. Liquidhope: methylome and genomic profiling from very limited quantities of plasma-derived DNA. Brief. Bioinform. 24, bbac575 (2023).

pubmed: 36611239 pmcid: 9851319 doi: 10.1093/bib/bbac575

Trinidad, E. M. et al. Evaluation of circulating tumor DNA by electropherogram analysis and methylome profiling in high-risk neuroblastomas. Front Oncol. 13, 1037342 (2023).

pubmed: 37251933 pmcid: 10213460 doi: 10.3389/fonc.2023.1037342

van der Laan, P., van Houdt, W. J., van den Broek, D., Steeghs, N. & van der Graaf, W. T. A. Liquid biopsies in sarcoma clinical practice: Where Do We Stand? Biomedicines 9, 1315 (2021).

High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN) (HR-NBL2), https://clinicaltrials.gov/study/NCT04221035 (2023).

Nakata, K., Colombet, M., Stiller, C. A., Pritchard-Jones, K. & Steliarova-Foucher, E. Incidence of childhood renal tumours: an international population-based study. Int J. Cancer 147, 3313–3327 (2020).

pubmed: 32902866 pmcid: 7689773 doi: 10.1002/ijc.33147

Ooms, A. et al. Renal tumors of childhood-a histopathologic pattern-based diagnostic approach. Cancers (Basel). 12, 729 (2020).

van den Heuvel-Eibrink, M. M. et al. Position paper: rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol. Nat. Rev. Urol. 14, 743–752 (2017).

pubmed: 29089605 doi: 10.1038/nrurol.2017.163

van der Beek, J. N. et al. Characteristics and outcome of children with renal cell carcinoma: a narrative review. Cancers (Basel). 12, 1776 (2020).

Gooskens, S. L. et al. Clear cell sarcoma of the kidney: a review. Eur. J. Cancer 48, 2219–2226 (2012).

pubmed: 22579455 doi: 10.1016/j.ejca.2012.04.009

Walz, A. L. et al. Tumor biology, biomarkers, and liquid biopsy in pediatric renal tumors. Pediatr. Blood Cancer 70, e30130 (2023).

pubmed: 36592003 doi: 10.1002/pbc.30130

Schulpen, M. et al. Incidence and survival of paediatric renal tumours in the Netherlands between 1990 and 2014. Eur. J. Cancer 175, 282–290 (2022).

pubmed: 36174300 doi: 10.1016/j.ejca.2022.08.021

Roy, P. et al. Characteristics and outcome of children with renal tumors in the Netherlands: the first five-year’s experience of national centralization. PLoS One 17, e0261729 (2022).

pubmed: 35025887 pmcid: 8757983 doi: 10.1371/journal.pone.0261729

Charlton, J., Pavasovic, V. & Pritchard-Jones, K. Biomarkers to detect Wilms tumors in pediatric patients: where are we now? Future Oncol. 11, 2221–2234, (2015).

pubmed: 26235184 doi: 10.2217/fon.15.136

Zheng, H., Liu, J., Pan, X. & Cui, X. Biomarkers for patients with Wilms tumor: a review. Front Oncol. 13, 1137346 (2023).

pubmed: 37554168 pmcid: 10405734 doi: 10.3389/fonc.2023.1137346

Huszno, J., Starzyczny-Słota, D., Jaworska, M. & Nowara, E. Adult Wilms’ tumor—diagnosis and current therapy. Cent. Eur. J. Urol. 66, 39–44 (2013).

doi: 10.5173/ceju.2013.01.art12

Jain, J., Sutton, K. S. & Hong, A. L. Progress update in pediatric renal tumors. Curr. Oncol. Rep. 23, 33 (2021).

pubmed: 33591402 doi: 10.1007/s11912-021-01016-y

Wang, J., Li, M., Tang, D., Gu, W., Mao, J., & Shu, Q. Current treatment for Wilms tumor: COG and SIOP standards. World J. Pediatr. Surg. 2, e000038 (2019).

Pater, L. et al. Wilms tumor. Pediatr. Blood Cancer 68, e28257 (2021).

pubmed: 32893998 doi: 10.1002/pbc.28257

Hol, J. A. et al. Prognostic significance of age in 5631 patients with Wilms tumour prospectively registered in International Society of Paediatric Oncology (SIOP) 93-01 and 2001. PLoS One 14, e0221373 (2019).

pubmed: 31425556 pmcid: 6699693 doi: 10.1371/journal.pone.0221373

Zekri, W., Yacoub, D. M., Ibrahim, A. & Madney, Y. Relapsed Wilms’ tumor in pediatric patients: challenges in low- to middle-income countries-a single-center experience. J. Egypt Natl. Canc. Inst. 32, 21 (2020).

pubmed: 32372372 doi: 10.1186/s43046-020-00032-6

Groenendijk, A. et al. Prognostic factors for Wilms tumor recurrence: a review of the literature. Cancers (Basel). 13, 3142 (2021).

Jackson, T. J. et al. How we approach paediatric renal tumour core needle biopsy in the setting of preoperative chemotherapy: a review from the SIOP Renal Tumour Study Group. Pediatr. Blood Cancer 69, e29702 (2022).

pubmed: 35587187 doi: 10.1002/pbc.29702

de Sa Pereira, B. M. et al. Intra-tumor genetic heterogeneity in Wilms tumor samples. Rev. Assoc. Med Bras. (1992) 65, 1496–1501 (2019).

pubmed: 31994632 doi: 10.1590/1806-9282.65.12.1496

Gadd, S. et al. A Children’s Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nat. Genet 49, 1487–1494 (2017).

pubmed: 28825729 pmcid: 5712232 doi: 10.1038/ng.3940

Grundy, P. E. et al. Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group. J. Clin. Oncol. 23, 7312–7321 (2005).

pubmed: 16129848 doi: 10.1200/JCO.2005.01.2799

Gratias, E. J. et al. Gain of 1q is associated with inferior event-free and overall survival in patients with favorable histology Wilms tumor: a report from the Children’s Oncology Group. Cancer 119, 3887–3894 (2013).

pubmed: 23983061 doi: 10.1002/cncr.28239

Madanat-Harjuoja, L. M. et al. Circulating tumor DNA as a biomarker in patients with stage III and IV Wilms tumor: analysis from a children’s oncology group trial, AREN0533. J. Clin. Oncol. 40, 3047–3056 (2022).

pubmed: 35580298 pmcid: 9462535 doi: 10.1200/JCO.22.00098

Jiménez, I. et al. Circulating tumor DNA analysis enables molecular characterization of pediatric renal tumors at diagnosis. Int. J. Cancer 144, 68–79 (2019).

pubmed: 29923174 doi: 10.1002/ijc.31620

Miguez, A. C. K. et al. Assessment of somatic mutations in urine and plasma of Wilms tumor patients. Cancer Med. 9, 5948–5959 (2020).

pubmed: 32592321 pmcid: 7433816 doi: 10.1002/cam4.3236

He, X. et al. Long non-coding RNA XIST promotes Wilms tumor progression through the miR-194-5p/YAP axis. Cancer Manag. Res. 13, 3171–3180 (2021).

pubmed: 33883934 pmcid: 8055356 doi: 10.2147/CMAR.S297842

Ludwig, N. et al. Circulating serum miRNAs as potential biomarkers for nephroblastoma. Pediatr. Blood Cancer 62, 1360–1367 (2015).

pubmed: 25787821 doi: 10.1002/pbc.25481

Schmitt, J. et al. Treatment-independent miRNA signature in blood of Wilms tumor patients. BMC Genom. 13, 379 (2012).

doi: 10.1186/1471-2164-13-379

Li, M. et al. Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application. Mol. Cancer 22, 37 (2023).

pubmed: 36810071 pmcid: 9942319 doi: 10.1186/s12943-023-01745-7

Salfer, B., Li, F., Wong, D. T. W. & Zhang, L. Urinary cell-free DNA in liquid biopsy and cancer management. Clin. Chem. 68, 1493–1501 (2022).

pubmed: 36213956 pmcid: 10423312 doi: 10.1093/clinchem/hvac122

Oshi, M. et al. Urine as a source of liquid biopsy for cancer. Cancers (Basel). 13, 2652 (2021).

Lin, R. Y., Argenta, P. A., Sullivan, K. M. & Adzick, N. S. Diagnostic and prognostic role of basic fibroblast growth factor in Wilms’ tumor patients. Clin. Cancer Res. 1, 327–331, (1995).

pubmed: 9815988

Stern, M., Longaker, M. T., Adzick, N. S., Harrison, M. R. & Stern, R. Hyaluronidase levels in urine from Wilms’ tumor patients. J. Natl. Cancer Inst. 83, 1569–1574, (1991).

pubmed: 1660075 doi: 10.1093/jnci/83.21.1569

Lin, R. Y., Argenta, P. A., Sullivan, K. M., Stern, R. & Adzick, N. S. Urinary hyaluronic acid is a Wilms’ tumor marker. J. Pediatr. Surg. 30, 304–308 (1995).

pubmed: 7738755 doi: 10.1016/0022-3468(95)90578-2

Ortiz, M. V. et al. Prohibitin is a prognostic marker and therapeutic target to block chemotherapy resistance in Wilms’ tumor. JCI Insight 4, e127098 (2019).

Weil, B. R. & Billmire, D. F. Management of germ cell tumors in pediatric patients. Surg. Oncol. Clin. N. Am. 30, 325–338 (2021).

pubmed: 33706903 doi: 10.1016/j.soc.2020.11.011

Oosterhuis, J. W. & Looijenga, L. H. J. Human germ cell tumours from a developmental perspective. Nat. Rev. Cancer 19, 522–537 (2019).

pubmed: 31413324 doi: 10.1038/s41568-019-0178-9

Pierce, J. L., Frazier, A. L. & Amatruda, J. F. Pediatric germ cell tumors: a developmental perspective. Adv. Urol. 2018, 9059382 (2018).

pubmed: 29515628 pmcid: 5817207 doi: 10.1155/2018/9059382

Egan, J. & Salari, K. Biomarkers in testicular cancer: classic tumor markers and beyond. Urol. Clin. North Am. 50, 133–143 (2023).

pubmed: 36424077 doi: 10.1016/j.ucl.2022.09.002

Kattuoa Ml, Dunton, C. J. Yolk Sac Tumors. In StatPearls [Internet]. Treasure Island (FL) (StatPearls Publishing, 2024). Available from: https://www.ncbi.nlm.nih.gov/books/NBK563163 /

Murray, M. J. et al. Circulating microRNAs as biomarkers to assist the management of the malignant germ-cell-tumour subtype choriocarcinoma. Transl. Oncol. 14, 100904 (2021).

pubmed: 33049521 doi: 10.1016/j.tranon.2020.100904

Lobo, J., Leao, R., Jeronimo, C. & Henrique, R. Liquid biopsies in the clinical management of germ cell tumor patients: state-of-the-art and future directions. Int. J. Mol. Sci. 22, 2654 (2021).

Nicholson, B. D. et al. The diagnostic performance of current tumour markers in surveillance for recurrent testicular cancer: A diagnostic test accuracy systematic review. Cancer Epidemiol. 59, 15–21 (2019).

pubmed: 30658216 doi: 10.1016/j.canep.2019.01.001

Murray, M. J. & Coleman, N. Testicular cancer: a new generation of biomarkers for malignant germ cell tumours. Nat. Rev. Urol. 9, 298–300 (2012).

pubmed: 22549310 doi: 10.1038/nrurol.2012.86

Almstrup, K. et al. Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours. Nat. Rev. Urol. 17, 201–213 (2020).

pubmed: 32157202 doi: 10.1038/s41585-020-0296-x

Jansson, M. D. & Lund, A. H. MicroRNA and cancer. Mol. Oncol. 6, 590–610 (2012).

pubmed: 23102669 pmcid: 5528350 doi: 10.1016/j.molonc.2012.09.006

Leao, R. et al. Circulating MicroRNAs, the next-generation serum biomarkers in testicular germ cell tumours: a systematic review. Eur. Urol. 80, 456–466 (2021).

pubmed: 34175151 doi: 10.1016/j.eururo.2021.06.006

Chovanec, M., Kalavska, K., Mego, M. & Cheng, L. Liquid biopsy in germ cell tumors: biology and clinical management. Expert Rev. Mol. Diagn. 20, 187–194 (2020).

pubmed: 31652083 doi: 10.1080/14737159.2019.1685383

Voorhoeve, P. M. et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124, 1169–1181 (2006).

pubmed: 16564011 doi: 10.1016/j.cell.2006.02.037

Dieckmann, K. P. et al. Serum levels of MicroRNA-371a-3p (M371 Test) as a new biomarker of testicular germ cell tumors: results of a prospective multicentric study. J. Clin. Oncol. 37, 1412–1423 (2019).

pubmed: 30875280 pmcid: 6544462 doi: 10.1200/JCO.18.01480

Gillis, A. J. et al. High-throughput microRNAome analysis in human germ cell tumours. J. Pathol. 213, 319–328 (2007).

pubmed: 17893849 doi: 10.1002/path.2230

Looijenga, L. H., Gillis, A. J., Stoop, H., Hersmus, R. & Oosterhuis, J. W. Relevance of microRNAs in normal and malignant development, including human testicular germ cell tumours. Int. J. Androl. 30, 304–314 (2007).

pubmed: 17573854 doi: 10.1111/j.1365-2605.2007.00765.x

Palmer, R. D. et al. Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets. Cancer Res. 70, 2911–2923 (2010).

pubmed: 20332240 pmcid: 3000593 doi: 10.1158/0008-5472.CAN-09-3301

Murray, M. J. et al. Identification of microRNAs From the miR-371~373 and miR-302 clusters as potential serum biomarkers of malignant germ cell tumors. Am. J. Clin. Pathol. 135, 119–125 (2011).

pubmed: 21173133 doi: 10.1309/AJCPOE11KEYZCJHT

Belge, G., Dieckmann, K. P., Spiekermann, M., Balks, T. & Bullerdiek, J. Serum levels of microRNAs miR-371-3: a novel class of serum biomarkers for testicular germ cell tumors? Eur. Urol. 61, 1068–1069, (2012).

pubmed: 22386195 doi: 10.1016/j.eururo.2012.02.037

Gillis, A. J. et al. Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: a proof of principle. Mol. Oncol. 7, 1083–1092 (2013).

pubmed: 24012110 pmcid: 5528443 doi: 10.1016/j.molonc.2013.08.002

Piao, J. et al. A multi-institutional pooled analysis demonstrates that circulating miR-371a-3p alone is sufficient for testicular malignant germ cell tumor diagnosis. Clin. Genitourin. Cancer 19, 469–479 (2021).

pubmed: 34629299 pmcid: 9084514 doi: 10.1016/j.clgc.2021.08.006

Murray, M. J. et al. A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours. Br. J. Cancer 114, 151–162 (2016).

pubmed: 26671749 doi: 10.1038/bjc.2015.429

Murray, M. J. et al. Clinical utility of circulating miR-371a-3p for the management of patients with intracranial malignant germ cell tumors. Neurooncol. Adv. 2, vdaa048 (2020).

pubmed: 32642701 pmcid: 7236383

Schonberger, S. et al. MicroRNA-profiling of miR-371~373- and miR-302/367-clusters in serum and cerebrospinal fluid identify patients with intracranial germ cell tumors. J. Cancer Res. Clin. Oncol. 149, 791–802 (2023).

pubmed: 35171328 doi: 10.1007/s00432-022-03915-4

Saliyeva, S., Boranbayeva, R., Bulegenova, M. & Beloussov, V. Application of microRNAs in the diagnosis and monitoring of pediatric germ cell tumors: Kazakh experience. Pediatr. Hematol. Oncol. 41, 1–14 (2023).

Multicenter prospective study of a randomized comparison of carboplatin with cisplatin in extracranial malignant germ cell tumors https://www.gpoh.de/kinderkrebsinfo/content/health_professionals/clinical_trials/therapy_trials_and_registries_in_the_gpoh/makei_v/index_eng.html (2024).

Magic Consortium AGCT1531 Clinical Trail, https://magicconsortium.com/magic-research/clinical-trials/ (2021).

Lobo, J. et al. Combining hypermethylated RASSF1A detection using ddPCR with miR-371a-3p testing: an improved panel of liquid biopsy biomarkers for testicular germ cell tumor patients. Cancers (Basel). 13, 5228 (2021).

Nappi, L. et al. Integrated expression of circulating miR375 and miR371 to identify teratoma and active germ cell malignancy components in malignant germ cell tumors. Eur. Urol. 79, 16–19 (2021).

pubmed: 33158661 doi: 10.1016/j.eururo.2020.10.024

Lobo, J. et al. Identification and validation model for informative liquid biopsy-based microRNA biomarkers: insights from germ cell tumor in vitro, in vivo and patient-derived data. Cells 8, 1637 (2019).

Lafin, J. T. et al. Serum small RNA sequencing and miR-375 assay do not identify the presence of pure teratoma at postchemotherapy retroperitoneal lymph node dissection. Eur. Urol. Open Sci. 26, 83–87 (2021).

pubmed: 33997822 pmcid: 8121258 doi: 10.1016/j.euros.2021.02.003

Belge, G., Grobelny, F., Matthies, C., Radtke, A. & Dieckmann, K. P. Serum level of microRNA-375-3p is not a reliable biomarker of teratoma. Vivo 34, 163–168 (2020).

doi: 10.21873/invivo.11757

Myklebust, M. P. et al. MicroRNAs in differentiation of embryoid bodies and the teratoma subtype of testicular cancer. Cancer Genom. Proteom. 19, 178–193 (2022).

doi: 10.21873/cgp.20313

Lafin, J. T. et al. Serum MicroRNA-371a-3p levels predict viable germ cell tumor in chemotherapy-naive patients undergoing retroperitoneal lymph node dissection. Eur. Urol. 77, 290–292 (2020).

pubmed: 31699528 doi: 10.1016/j.eururo.2019.10.005

Eaton, B. R. et al. Osteosarcoma. Pediatr. Blood Cancer 68, e28352 (2021).

pubmed: 32779875 doi: 10.1002/pbc.28352

Beird, H. C. et al. Osteosarcoma. Nat. Rev. Dis. Prim. 8, 77 (2022).

pubmed: 36481668 doi: 10.1038/s41572-022-00409-y

Aran, V. et al. Osteosarcoma, chondrosarcoma and Ewing sarcoma: clinical aspects, biomarker discovery and liquid biopsy. Crit. Rev. Oncol. Hematol. 162, 103340 (2021).

pubmed: 33894338 doi: 10.1016/j.critrevonc.2021.103340

Ritter, J. & Bielack, S. S. Osteosarcoma. Ann. Oncol. 21, vii320–vii325 (2010).

pubmed: 20943636 doi: 10.1093/annonc/mdq276

Odri, G. A., Tchicaya-Bouanga, J., Yoon, D. J. Y. & Modrowski, D. Metastatic progression of osteosarcomas: a review of current knowledge of environmental versus oncogenic drivers. Cancers (Basel). 14, 360 (2022).

Ucci, A., Rucci, N. & Ponzetti, M. Liquid biopsies in primary and secondary bone cancers. Cancer Drug Resist 5, 541–559 (2022).

pubmed: 36176757 pmcid: 9511800 doi: 10.20517/cdr.2022.17

Barris, D. M. et al. Detection of circulating tumor DNA in patients with osteosarcoma. Oncotarget 9, 12695–12704 (2018).

pubmed: 29560102 pmcid: 5849166 doi: 10.18632/oncotarget.24268

Bao, Q. et al. Extracellular vesicle RNA sequencing reveals dramatic transcriptomic alterations between metastatic and primary osteosarcoma in a liquid biopsy approach. Ann. Surg. Oncol. 25, 2642–2651 (2018).

pubmed: 29981024 doi: 10.1245/s10434-018-6642-z

Lyskjær, I. et al. Osteosarcoma: novel prognostic biomarkers using circulating and cell-free tumour DNA. Eur. J. Cancer 168, 1–11 (2022).

pubmed: 35421838 doi: 10.1016/j.ejca.2022.03.002

Kurihara, S. et al. Circulating free DNA as non-invasive diagnostic biomarker for childhood solid tumors. J. Pediatr. Surg. 50, 2094–2097 (2015).

pubmed: 26388126 doi: 10.1016/j.jpedsurg.2015.08.033

Van Paemel, R. et al. Minimally invasive classification of paediatric solid tumours using reduced representation bisulphite sequencing of cell-free DNA: a proof-of-principle study. Epigenetics 16, 196–208 (2021).

pubmed: 32662719 doi: 10.1080/15592294.2020.1790950

Shah, A. T. et al. A comprehensive circulating tumor DNA assay for detection of translocation and copy-number changes in pediatric sarcomas. Mol. Cancer Ther. 20, 2016–2025 (2021).

pubmed: 34353895 pmcid: 9307079 doi: 10.1158/1535-7163.MCT-20-0987

Shulman, D. S. et al. Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children’s Oncology Group. Br. J. Cancer 119, 615–621 (2018).

pubmed: 30131550 pmcid: 6162271 doi: 10.1038/s41416-018-0212-9

Gai, W. & Sun, K. Epigenetic biomarkers in cell-free DNA and applications in liquid biopsy. Genes (Basel) 10, 32 (2019).

Li, M. et al. Prognostic and clinicopathological significance of circulating tumor cells in osteosarcoma. J. Bone Oncol. 16, 100236 (2019).

pubmed: 31024791 pmcid: 6475710 doi: 10.1016/j.jbo.2019.100236

Wu, Z. J., Tan, J. C., Qin, X., Liu, B. & Yuan, Z. C. Significance of circulating tumor cells in osteosarcoma patients treated by neoadjuvant chemotherapy and surgery. Cancer Manag. Res. 10, 3333–3339 (2018).

pubmed: 30237736 pmcid: 6138968 doi: 10.2147/CMAR.S176515

Sharma, S. et al. Circulating tumor cell isolation, culture, and downstream molecular analysis. Biotechnol. Adv. 36, 1063–1078 (2018).

pubmed: 29559380 pmcid: 5971144 doi: 10.1016/j.biotechadv.2018.03.007

Dai, S. et al. Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma. Front Oncol. 13, 819357 (2023).

pubmed: 36937398 pmcid: 10021108 doi: 10.3389/fonc.2023.819357

Zhang, H. Q. et al. [Detection and clinical significance of circulating tumor cells in osteosarcoma using immunofluorescence combined with in situ hybridization]. Zhonghua Zhong Liu Za Zhi 39, 485–489 (2017).

pubmed: 28728292

Zhang, H. et al. A liquid biopsy-based method for the detection and quantification of circulating tumor cells in surgical osteosarcoma patients. Int J. Oncol. 50, 1075–1086 (2017).

pubmed: 28350107 pmcid: 5363882 doi: 10.3892/ijo.2017.3905

Jawad, M. U. & Scully, S. P. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin. Orthop. Relat. Res. 468, 2000–2002, (2010).

pubmed: 20333492 pmcid: 2882012 doi: 10.1007/s11999-010-1315-7

Xie, X. Y., Chen, X. M., Shi, L. & Liu, J. W. Increased expression of microRNA-26a-5p predicted a poor survival outcome in osteosarcoma patients: an observational study. Medicine (Baltimore) 100, e24765 (2021).

pubmed: 33761638 doi: 10.1097/MD.0000000000024765

Raimondi, L. et al. Circulating biomarkers in osteosarcoma: new translational tools for diagnosis and treatment. Oncotarget 8, 100831–100851 (2017).

pubmed: 29246026 pmcid: 5725068 doi: 10.18632/oncotarget.19852

Moonmuang, S., Chaiyawat, P., Jantrapirom, S., Pruksakorn, D. & Lo Piccolo, L. Circulating long non-coding RNAs as novel potential biomarkers for osteogenic sarcoma. Cancers (Basel). 13, 4214 (2021).

Gally, T. B., Aleluia, M. M., Borges, G. F. & Kaneto, C. M. Circulating MicroRNAs as novel potential diagnostic biomarkers for osteosarcoma: a systematic review. Biomolecules 11, 1432 (2021).

Wang, Y. et al. Diagnostic and prognostic value of circulating miR-21 for cancer: a systematic review and meta-analysis. Gene 533, 389–397 (2014).

pubmed: 24076132 doi: 10.1016/j.gene.2013.09.038

Dean, D. C., Shen, S., Hornicek, F. J. & Duan, Z. From genomics to metabolomics: emerging metastatic biomarkers in osteosarcoma. Cancer Metastasis Rev. 37, 719–731 (2018).

pubmed: 30167827 doi: 10.1007/s10555-018-9763-8

Liu, H. et al. MicroRNAs as a novel class of diagnostic biomarkers for the detection of osteosarcoma: a meta-analysis. Onco Targets Ther. 10, 5229–5236 (2017).

pubmed: 29138575 pmcid: 5677380 doi: 10.2147/OTT.S143974

Zhang, J. et al. MicroRNAs in osteosarcoma. Clin. Chim. Acta 444, 9–17 (2015).

pubmed: 25661090 doi: 10.1016/j.cca.2015.01.025

Gao, S. S., Wang, Y. J., Zhang, G. X. & Zhang, W. T. Potential diagnostic value of miRNAs in peripheral blood for osteosarcoma: a meta-analysis. J. Bone Oncol. 23, 100307 (2020).

pubmed: 32742918 pmcid: 7385506 doi: 10.1016/j.jbo.2020.100307

Wang, S., Ma, F., Feng, Y., Liu, T. & He, S. Role of exosomal miR‑21 in the tumor microenvironment and osteosarcoma tumorigenesis and progression (Review). Int. J. Oncol. 56, 1055–1063 (2020).

pubmed: 32319566

Grünewald, T. G. P. et al. Ewing sarcoma. Nat. Rev. Dis. Prim. 4, 5 (2018).

pubmed: 29977059 doi: 10.1038/s41572-018-0003-x

Lin, P. P., Wang, Y. & Lozano, G. Mesenchymal stem cells and the origin of Ewing’s sarcoma. Sarcoma 2011, 276463 (2011).

Tu, J. et al. The histogenesis of Ewing sarcoma. Cancer Rep. Rev. 1, 1-4 (2017).

Khan, S. et al. Incidence of Ewing’s sarcoma in different age groups, their associated features, and its correlation with primary care interval. Cureus 13, e13986 (2021).

pubmed: 33884237 pmcid: 8054948

Zhang, P., Samuel, G., Crow, J., Godwin, A. K. & Zeng, Y. Molecular assessment of circulating exosomes toward liquid biopsy diagnosis of Ewing sarcoma family of tumors. Transl. Res. 201, 136–153 (2018).

pubmed: 30031766 pmcid: 6424494 doi: 10.1016/j.trsl.2018.05.007

Cervera, S. T. et al. Therapeutic potential of EWSR1-FLI1 inactivation by CRISPR/Cas9 in Ewing sarcoma. Cancers (Basel). 13, 3783 (2021).

Crow, J. et al. MicroRNA content of Ewing sarcoma derived extracellular vesicles leads to biomarker potential and identification of a previously undocumented EWS-FLI1 translocation. Biomark. Insights 17, 11772719221132693 (2022).

pubmed: 36341281 pmcid: 9629554 doi: 10.1177/11772719221132693

West, D. C. et al. Detection of circulating tumor cells in patients with Ewing’s sarcoma and peripheral primitive neuroectodermal tumor. J. Clin. Oncol. 15, 583–588 (1997).

pubmed: 9053480 doi: 10.1200/JCO.1997.15.2.583

Zoubek, A. et al. Predictive potential of testing for bone marrow involvement in Ewing tumor patients by RT-PCR: a preliminary evaluation. Int. J. Cancer 79, 56–60 (1998).

pubmed: 9495359 doi: 10.1002/(SICI)1097-0215(19980220)79:1<56::AID-IJC11>3.0.CO;2-F

Fagnou, C. et al. Presence of tumor cells in bone marrow but not in blood is associated with adverse prognosis in patients with Ewing’s tumor. Société Française d’Oncologie Pédiatrique. J. Clin. Oncol. 16, 1707–1711 (1998).

pubmed: 9586882 doi: 10.1200/JCO.1998.16.5.1707

de Alava, E., Lozano, M. D., Patiño, A., Sierrasesúmaga, L. & Pardo-Mindán, F. J. Ewing family tumors: potential prognostic value of reverse-transcriptase polymerase chain reaction detection of minimal residual disease in peripheral blood samples. Diagn. Mol. Pathol. 7, 152–157 (1998).

pubmed: 9836070 doi: 10.1097/00019606-199806000-00005

Athale, U. H. et al. Use of reverse transcriptase polymerase chain reaction for diagnosis and staging of alveolar rhabdomyosarcoma, Ewing sarcoma family of tumors, and desmoplastic small round cell tumor. J. Pediatr. Hematol. Oncol. 23, 99–104 (2001).

pubmed: 11216714 doi: 10.1097/00043426-200102000-00006

Schleiermacher, G. et al. Increased risk of systemic relapses associated with bone marrow micrometastasis and circulating tumor cells in localized Ewing tumor. J. Clin. Oncol. 21, 85–91 (2003).

pubmed: 12506175 doi: 10.1200/JCO.2003.03.006

Rizk, V. T., Walko, C. M. & Brohl, A. S. Precision medicine approaches for the management of Ewing sarcoma: current perspectives. Pharmgenom. Pers. Med 12, 9–14 (2019).

Krumbholz, M. et al. Quantification of translocation-specific ctDNA provides an integrating parameter for early assessment of treatment response and risk stratification in Ewing sarcoma. Clin. Cancer Res. 27, 5922–5930 (2021).

pubmed: 34426444 doi: 10.1158/1078-0432.CCR-21-1324

Schmidkonz, C. et al. Assessment of treatment responses in children and adolescents with Ewing sarcoma with metabolic tumor parameters derived from (18)F-FDG-PET/CT and circulating tumor DNA. Eur. J. Nucl. Med. Mol. Imaging 47, 1564–1575 (2020).

pubmed: 31853559 doi: 10.1007/s00259-019-04649-1

Seidel, M. G. et al. Clinical implementation of plasma cell-free circulating tumor DNA quantification by digital droplet PCR for the monitoring of Ewing sarcoma in children and adolescents. Front Pediatr. 10, 926405 (2022).

pubmed: 36046479 pmcid: 9420963 doi: 10.3389/fped.2022.926405

Allegretti, M. et al. Precision diagnostics of Ewing’s sarcoma by liquid biopsy: circulating EWS-FLI1 fusion transcripts. Ther. Adv. Med. Oncol. 10, 1758835918774337 (2018).

pubmed: 29899761 pmcid: 5985603 doi: 10.1177/1758835918774337

Samuel, G. et al. Ewing sarcoma family of tumors-derived small extracellular vesicle proteomics identify potential clinical biomarkers. Oncotarget 11, 2995–3012 (2020).

pubmed: 32821345 pmcid: 7415402 doi: 10.18632/oncotarget.27678

Bodlak, A. et al. Circulating plasma tumor DNA is superior to plasma tumor RNA detection in Ewing sarcoma patients: ptDNA and ptRNA in Ewing sarcoma. J. Mol. Diagn. 23, 872–881 (2021).

pubmed: 33887462 pmcid: 8261897 doi: 10.1016/j.jmoldx.2021.04.003

Tanaka, K., Iwakuma, T., Harimaya, K., Sato, H. & Iwamoto, Y. EWS-Fli1 antisense oligodeoxynucleotide inhibits proliferation of human Ewing’s sarcoma and primitive neuroectodermal tumor cells. J. Clin. Invest 99, 239–247 (1997).

pubmed: 9005992 pmcid: 507791 doi: 10.1172/JCI119152

Erkizan, H. V. et al. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing’s sarcoma. Nat. Med 15, 750–756 (2009).

pubmed: 19584866 pmcid: 2777681 doi: 10.1038/nm.1983

Salguero-Aranda, C., Amaral, A. T., Olmedo-Pelayo, J., Diaz-Martin, J. & Álava, E. Breakthrough technologies reshape the Ewing sarcoma molecular landscape. Cells 9 (2020).

International Euro Ewing Trial for Treatmentoptimisation in Patients with Ewing Sarcoma, https://www.gpoh.de/kinderkrebsinfo/content/fachinformationen/studienportal/onkologische_studien_und_register/ieuroewing/index_ger.html (2024).

International clinical research programme to improve outcomes in newly diagnosed Ewing sarcoma – Trial 1, https://www.isrctn.com/ISRCTN17938906 (2023).

Skapek, S. X. et al. Rhabdomyosarcoma. Nat. Rev. Dis. Prim. 5, 1 (2019).

pubmed: 30617281 doi: 10.1038/s41572-018-0051-2

Dasgupta, R., Fuchs, J. & Rodeberg, D. Rhabdomyosarcoma. Semin Pediatr. Surg. 25, 276–283 (2016).

pubmed: 27955730 doi: 10.1053/j.sempedsurg.2016.09.011

Kaseb, H., Kuhn, J., Gasalberti, D. P. et al. Rhabdomyosarcoma. In StatPearls [Internet]. Treasure Island (FL) (StatPearls Publishing, 2024). Available from: https://www.ncbi.nlm.nih.gov/books/NBK507721/

Miwa, S. et al. Recent advances and challenges in the treatment of rhabdomyosarcoma. Cancers (Basel). 12, 1758 (2020).

Hettmer, S. et al. Molecular testing of rhabdomyosarcoma in clinical trials to improve risk stratification and outcome: a consensus view from European paediatric Soft tissue sarcoma Study Group, Children’s Oncology Group and Cooperative Weichteilsarkom-Studiengruppe. Eur. J. Cancer 172, 367–386 (2022).

pubmed: 35839732 doi: 10.1016/j.ejca.2022.05.036

Oberlin, O. et al. Prognostic factors in metastatic rhabdomyosarcomas: results of a pooled analysis from United States and European cooperative groups. J. Clin. Oncol. 26, 2384–2389 (2008).

pubmed: 18467730 pmcid: 4558625 doi: 10.1200/JCO.2007.14.7207

Ouchi, K. et al. Oncogenic role of HMGA2 in fusion-negative rhabdomyosarcoma cells. Cancer Cell Int. 20, 192 (2020).

pubmed: 32489328 pmcid: 7247181 doi: 10.1186/s12935-020-01282-z

Lak, N. S. M. et al. Improving risk stratification for pediatric patients with rhabdomyosarcoma by molecular detection of disseminated disease. Clin. Cancer Res. 27, 5576–5585 (2021).

pubmed: 34285060 pmcid: 9401561 doi: 10.1158/1078-0432.CCR-21-1083

Wang, C. Childhood rhabdomyosarcoma: recent advances and prospective views. J. Dent. Res. 91, 341–350, (2012).

pubmed: 21917598 pmcid: 3310752 doi: 10.1177/0022034511421490

Leiner, J. & Le Loarer, F. The current landscape of rhabdomyosarcomas: an update. Virchows Arch. 476, 97–108 (2020).

pubmed: 31696361 doi: 10.1007/s00428-019-02676-9

Williamson, D. et al. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J. Clin. Oncol. 28, 2151–2158 (2010).

pubmed: 20351326 doi: 10.1200/JCO.2009.26.3814

Hibbitts, E. et al. Refinement of risk stratification for childhood rhabdomyosarcoma using FOXO1 fusion status in addition to established clinical outcome predictors: A report from the Children’s Oncology Group. Cancer Med 8, 6437–6448 (2019).

pubmed: 31456361 pmcid: 6797586 doi: 10.1002/cam4.2504

Gallego, S. et al. Fusion status in patients with lymph node-positive (N1) alveolar rhabdomyosarcoma is a powerful predictor of prognosis: Experience of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG). Cancer 124, 3201–3209 (2018).

pubmed: 29797665 doi: 10.1002/cncr.31553

Heske, C. M. et al. Survival outcomes of patients with localized FOXO1 fusion-positive rhabdomyosarcoma treated on recent clinical trials: A report from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Cancer 127, 946–956 (2021).

pubmed: 33216382 doi: 10.1002/cncr.33334

Michelagnoli, M. P., Burchill, S. A., Cullinane, C., Selby, P. J. & Lewis, I. J. Myogenin–a more specific target for RT-PCR detection of rhabdomyosarcoma than MyoD1. Med. Pediatr. Oncol. 40, 1–8 (2003).

pubmed: 12426678 doi: 10.1002/mpo.10201

Gallego, S. et al. Detection of bone marrow micrometastasis and microcirculating disease in rhabdomyosarcoma by a real-time RT-PCR assay. J. Cancer Res. Clin. Oncol. 132, 356–362 (2006).

pubmed: 16435141 doi: 10.1007/s00432-006-0083-y

Sartori, F. et al. Results of a prospective minimal disseminated disease study in human rhabdomyosarcoma using three different molecular markers. Cancer 106, 1766–1775 (2006).

pubmed: 16544315 doi: 10.1002/cncr.21772

Krskova, L. et al. Detection and clinical significance of bone marrow involvement in patients with rhabdomyosarcoma. Virchows Arch. 456, 463–472 (2010).

pubmed: 20405298 doi: 10.1007/s00428-010-0913-9

Ruhen, O. et al. Molecular characterization of circulating tumor DNA in pediatric rhabdomyosarcoma: a feasibility study. JCO Precis. Oncol. 6, e2100534 (2022).

pubmed: 36265118 pmcid: 9616639 doi: 10.1200/PO.21.00534

Abbou, S. et al. Circulating tumor DNA is prognostic in intermediate-risk rhabdomyosarcoma: a report from the children’s oncology group. J. Clin. Oncol. 41, 2382–2393 (2023).

pubmed: 36724417 pmcid: 10150913 doi: 10.1200/JCO.22.00409

Lak, N. S. M. et al. Cell-free DNA as a diagnostic and prognostic biomarker in pediatric rhabdomyosarcoma. JCO Precis. Oncol. 7, e2200113 (2023).

pubmed: 36652664 pmcid: 9928631 doi: 10.1200/PO.22.00113

Poli, E. et al. Prognostic value of circulating IGFBP2 and related autoantibodies in children with metastatic rhabdomyosarcomas. Diagnostics (Basel) 10, 115 (2020).

Urla, C. et al. Epitope Detection in Monocytes (EDIM) as a new method of liquid biopsy in pediatric rhabdomyosarcoma. Biomedicines 10, 1812 (2022).

de Traux de Wardin, H. et al. Sequential genomic analysis using a multisample/multiplatform approach to better define rhabdomyosarcoma progression and relapse. NPJ Precis. Oncol. 7, 96 (2023).

pubmed: 37730754 pmcid: 10511463 doi: 10.1038/s41698-023-00445-1

Hayashi, M. et al. Size-based detection of sarcoma circulating tumor cells and cell clusters. Oncotarget 8, 78965–78977 (2017).

pubmed: 29108279 pmcid: 5668012 doi: 10.18632/oncotarget.20697

Eguchi-Ishimae, M. et al. Early detection of the PAX3-FOXO1 fusion gene in circulating tumor-derived DNA in a case of alveolar rhabdomyosarcoma. Genes Chromosomes. Cancer 58, 521–529 (2019).

pubmed: 30739374 doi: 10.1002/gcc.22734

Tombolan, L. et al. Clinical significance of circulating tumor cells and cell-free DNA in pediatric rhabdomyosarcoma. Mol. Oncol. 16, 2071–2085 (2022).

pubmed: 35212153 pmcid: 9120897 doi: 10.1002/1878-0261.13197

Stegmaier, S. et al. Fusion transcripts as liquid biopsy markers in alveolar rhabdomyosarcoma and synovial sarcoma: A report of the Cooperative Weichteilsarkom Studiengruppe (CWS). Pediatr. Blood Cancer 69, e29652 (2022).

pubmed: 35338758 doi: 10.1002/pbc.29652

FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS), https://clinicaltrials.gov/study/NCT04625907 (2023).

Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma, https://clinicaltrials.gov/study/NCT02567435 (2024).

Ferrari, A. et al. Paediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG). Lancet Child Adolesc. Health 5, 546–558 (2021).

pubmed: 34214481 doi: 10.1016/S2352-4642(21)00159-0

Waxweiler, T. V. et al. Non-rhabdomyosarcoma soft tissue sarcomas in children: a surveillance, epidemiology, and end results analysis validating COG risk stratifications. Int. J. Radiat. Oncol. Biol. Phys. 92, 339–348 (2015).

pubmed: 25968827 doi: 10.1016/j.ijrobp.2015.02.007

Ferrari, A. et al. Pediatric non-rhabdomyosarcoma soft tissue sarcomas: standard of care and treatment recommendations from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG). Cancer Manag Res 14, 2885–2902 (2022).

pubmed: 36176694 pmcid: 9514781 doi: 10.2147/CMAR.S368381

Ferrari, A. et al. Soft tissue sarcoma across the age spectrum: a population-based study from the Surveillance Epidemiology and End Results database. Pediatr. Blood Cancer 57, 943–949 (2011).

pubmed: 21793180 pmcid: 4261144 doi: 10.1002/pbc.23252

Qureshi, S. S. & Bhagat, M. Non-rhabdomyosarcoma soft-tissue sarcomas in children: contemporary appraisal and experience from a single centre. J. Indian Assoc. Pediatr. Surg. 20, 165–169 (2015).

pubmed: 26628806 pmcid: 4586977 doi: 10.4103/0971-9261.154664

Venkatramani, R. et al. Synovial sarcoma in children, adolescents, and young adults: a report from the children’s oncology group ARST0332 study. J. Clin. Oncol. 39, 3927–3937 (2021).

pubmed: 34623899 pmcid: 8660012 doi: 10.1200/JCO.21.01628

Ferrari, A. et al. Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: a cohort study from the European paediatric Soft tissue sarcoma Study Group. Cancer 129, 2542–2552 (2023).

pubmed: 37084075 doi: 10.1002/cncr.34814

Alix-Panabières, C., Marchetti, D. & Lang, J. E. Liquid biopsy: from concept to clinical application. Sci. Rep. 13, 21685 (2023).

pubmed: 38066040 pmcid: 10709452 doi: 10.1038/s41598-023-48501-x

Mertens, F., Antonescu, C. R. & Mitelman, F. Gene fusions in soft tissue tumors: Recurrent and overlapping pathogenetic themes. Genes Chromosomes Cancer 55, 291–310 (2016).

pubmed: 26684580 doi: 10.1002/gcc.22335

Shukla, N. N. et al. Plasma DNA-based molecular diagnosis, prognostication, and monitoring of patients with EWSR1 fusion-positive sarcomas. JCO Precis. Oncol. 2017, 1–11 (2017).

Uotani, K. et al. Circulating MicroRNA-92b-3p as a novel biomarker for monitoring of synovial sarcoma. Sci. Rep. 7, 14634 (2017).

pubmed: 29116117 pmcid: 5676745 doi: 10.1038/s41598-017-12660-5

Yokoo, S. et al. Liquid biopsy targeting monocarboxylate transporter 1 on the surface membrane of tumor-derived extracellular vesicles from synovial sarcoma. Cancers (Basel). 13, 1823 (2021).

Szymanski, J. J. et al. Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: a cross-sectional study. PLoS Med 18, e1003734 (2021).

pubmed: 34464388 pmcid: 8407545 doi: 10.1371/journal.pmed.1003734

Wakely, P. E. Jr. Cytopathology of classic type epithelioid sarcoma: a series of 20 cases and review of the literature. J. Am. Soc. Cytopathol. 9, 126–136 (2020).

pubmed: 32113803 doi: 10.1016/j.jasc.2019.11.001

Viñal, D. et al. Prognostic value of neutrophil-to-lymphocyte ratio and other inflammatory markers in patients with high-risk soft tissue sarcomas. Clin. Transl. Oncol. 22, 1849–1856 (2020).

pubmed: 32125644 doi: 10.1007/s12094-020-02324-8

Que, Y. et al. Preoperative platelet-lymphocyte ratio is superior to neutrophil-lymphocyte ratio as a prognostic factor for soft-tissue sarcoma. BMC Cancer 15, 648 (2015).

pubmed: 26432433 pmcid: 4592563 doi: 10.1186/s12885-015-1654-6

Park, S. J. et al. Serum biomarkers for neurofibromatosis type 1 and early detection of malignant peripheral nerve-sheath tumors. BMC Med 11, 109 (2013).

pubmed: 23618374 pmcid: 3648455 doi: 10.1186/1741-7015-11-109

Hummel, T. R. et al. Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. Clin. Cancer Res. 16, 5048–5057 (2010).

pubmed: 20739432 pmcid: 4837895 doi: 10.1158/1078-0432.CCR-10-0613

Chen, S. et al. Prognostic analysis of surgically treated clear cell sarcoma: an analysis of a rare tumor from a single center. Int. J. Clin. Oncol. 24, 1605–1611 (2019).

pubmed: 31243628 pmcid: 6861539 doi: 10.1007/s10147-019-01487-x

Bottillo, I. et al. Germline and somatic NF1 mutations in sporadic and NF1-associated malignant peripheral nerve sheath tumours. J. Pathol. 217, 693–701 (2009).

pubmed: 19142971 doi: 10.1002/path.2494

Arshad, J. et al. Utility of circulating tumor DNA in the management of patients with GI stromal tumor: analysis of 243 patients. JCO Precis. Oncol. 4, 66–73 (2020).

pubmed: 35050730 doi: 10.1200/PO.19.00253

Sultan, I. et al. Comparing children and adults with synovial sarcoma in the Surveillance, Epidemiology, and End Results program, 1983 to 2005: an analysis of 1268 patients. Cancer 115, 3537–3547 (2009).

pubmed: 19514087 doi: 10.1002/cncr.24424

Colletti, M. et al. Expression profiles of exosomal miRNAs isolated from plasma of patients with desmoplastic small round cell tumor. Epigenomics 11, 489–500 (2019).

pubmed: 30569756 doi: 10.2217/epi-2018-0179

Peneder, P. et al. Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden. Nat. Commun. 12, 3230 (2021).

pubmed: 34050156 pmcid: 8163828 doi: 10.1038/s41467-021-23445-w

Tombolan, L. et al. Pediatric sarcomas display a variable EpCAM expression in a histology-dependent manner. Transl. Oncol. 13, 100846 (2020).

pubmed: 32805674 pmcid: 7453064 doi: 10.1016/j.tranon.2020.100846

MyKids: molecular profiling of non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) in children, adolescents and young adults, https://www.isrctn.com/ISRCTN12831761 (2022).

Ranganathan, S., Lopez-Terrada, D. & Alaggio, R. Hepatoblastoma and pediatric hepatocellular carcinoma: an update. Pediatr. Dev. Pathol. 23, 79–95 (2020).

pubmed: 31554479 doi: 10.1177/1093526619875228

Ng, K. & Mogul, D. B. Pediatric liver tumors. Clin. Liver Dis. 22, 753–772 (2018).

pubmed: 30266161 doi: 10.1016/j.cld.2018.06.008

Geramizadeh, B., Foroughi, R. & Shojazadeh, A. Hepatocellular malignant neoplasm, not otherwise specified: a new name in liver tumors: a brief narrative review of published cases. Gastrointest. Tumors 8, 96–100 (2021).

pubmed: 33981688 pmcid: 8077602 doi: 10.1159/000513962

Crippa, S. et al. Mutant CTNNB1 and histological heterogeneity define metabolic subtypes of hepatoblastoma. EMBO Mol. Med. 9, 1589–1604 (2017).

pubmed: 28923827 pmcid: 5666308 doi: 10.15252/emmm.201707814

Varol, F. I. Pediatric hepatocellular carcinoma. J. Gastrointest. Cancer 51, 1169–1175 (2020).

pubmed: 32856229 doi: 10.1007/s12029-020-00494-w

Espinoza, A. F. et al. An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer. bioRxiv, (2023).

Carr, B. I. et al. HCC with low- and normal-serum alpha-fetoprotein levels. Clin. Pract. (Lond.) 15, 453–464 (2018).

pubmed: 29576865

Rabbani, T., Bartlett, J. M. A. & Mittal, N. Liver biopsy in children. Indian Pediatr. 57, 734–740 (2020).

pubmed: 32844759 doi: 10.1007/s13312-020-1918-3

Liu, W., Chen, S. & Liu, B. Diagnostic and prognostic values of serum exosomal microRNA-21 in children with hepatoblastoma: a Chinese population-based study. Pediatr. Surg. Int. 32, 1059–1065 (2016).

pubmed: 27601233 doi: 10.1007/s00383-016-3960-8

Jiao, C., Jiao, X., Zhu, A., Ge, J. & Xu, X. Exosomal miR-34s panel as potential novel diagnostic and prognostic biomarker in patients with hepatoblastoma. J. Pediatr. Surg. 52, 618–624 (2017).

pubmed: 28277300 doi: 10.1016/j.jpedsurg.2016.09.070

Maurya, P., Meleady, P., Dowling, P. & Clynes, M. Proteomic approaches for serum biomarker discovery in cancer. Anticancer Res. 27, 1247–1255, (2007).

pubmed: 17593616

Zhao, W. et al. Screening and identification of apolipoprotein A-I as a potential hepatoblastoma biomarker in children, excluding inflammatory factors. Oncol. Lett. 10, 233–239 (2015).

pubmed: 26171005 pmcid: 4487141 doi: 10.3892/ol.2015.3207

Kahana-Edwin, S. et al. Exploration of CTNNB1 ctDNA as a putative biomarker for hepatoblastoma. Pediatr. Blood Cancer 67, e28594 (2020).

pubmed: 32881242 doi: 10.1002/pbc.28594

Visal, T. H., den Hollander, P., Cristofanilli, M. & Mani, S. A. Circulating tumour cells in the -omics era: how far are we from achieving the ‘singularity’? Br. J. Cancer 127, 173–184 (2022).

pubmed: 35273384 pmcid: 9296521 doi: 10.1038/s41416-022-01768-9

Kim, E. S. et al. Potential utility of risk stratification for multicancer screening with liquid biopsy tests. NPJ Precis. Oncol. 7, 39 (2023).

pubmed: 37087533 pmcid: 10122653 doi: 10.1038/s41698-023-00377-w

Tie, J. et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N. Engl. J. Med. 386, 2261–2272 (2022).

pubmed: 35657320 pmcid: 9701133 doi: 10.1056/NEJMoa2200075

Cho, H. W. et al. Treatment outcomes in children and adolescents with relapsed or progressed solid tumors: a 20-year, single-center study. J. Korean Med Sci. 33, e260 (2018).

pubmed: 30288158 pmcid: 6170668 doi: 10.3346/jkms.2018.33.e260

Pieters, R. et al. Successful therapy reduction and intensification for childhood acute lymphoblastic leukemia based on minimal residual disease monitoring: study ALL10 from the dutch childhood oncology group. J. Clin. Oncol. 34, 2591–2601 (2016).

pubmed: 27269950 doi: 10.1200/JCO.2015.64.6364

Pieters, R. et al. Dutch ALL11 study: improved outcome for acute lymphoblastic leukemia by prolonging therapy for IKZF1 deletion and decreasing therapy for ETV6::RUNX1, down syndrome and prednisone poor responders. Blood 140, 519–520 (2022).

doi: 10.1182/blood-2022-165931

Chicard, M. et al. Whole-exome sequencing of cell-free DNA reveals temporo-spatial heterogeneity and identifies treatment-resistant clones in neuroblastoma. Clin. Cancer Res. 24, 939–949 (2018).

pubmed: 29191970 doi: 10.1158/1078-0432.CCR-17-1586

Remon, J. et al. Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA. Ann. Oncol. 28, 784–790 (2017).

pubmed: 28104619 doi: 10.1093/annonc/mdx017

Bertacca, I., Pegoraro, F., Tondo, A. & Favre, C. Targeted treatment of solid tumors in pediatric precision oncology. Front Oncol. 13, 1176790 (2023).

pubmed: 37213274 pmcid: 10196192 doi: 10.3389/fonc.2023.1176790

Dawson, S. J. et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N. Engl. J. Med 368, 1199–1209 (2013).

pubmed: 23484797 doi: 10.1056/NEJMoa1213261

Tie, J. et al. Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study. Gut 68, 663–671 (2019).

pubmed: 29420226 doi: 10.1136/gutjnl-2017-315852

Chaudhuri, A. A. et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov. 7, 1394–1403 (2017).

pubmed: 28899864 pmcid: 5895851 doi: 10.1158/2159-8290.CD-17-0716

Henriksen, T. V. V. et al. Serial circulating tumor DNA analysis to assess recurrence risk, benefit of adjuvant therapy, growth rate and early relapse detection in stage III colorectal cancer patients. J. Clin. Oncol. 39, 3540–3540 (2021).

doi: 10.1200/JCO.2021.39.15_suppl.3540

Powles, T. et al. ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature 595, 432–437 (2021).

pubmed: 34135506 doi: 10.1038/s41586-021-03642-9

Karley, D., Gupta, D. & Tiwari, A. Biomarker for cancer: a great promise for future. World J. Oncol. 2, 151–157 (2011).

pubmed: 29147241 pmcid: 5649652

Novetsky Friedman, D. et al. Clonal hematopoiesis in survivors of childhood cancer. Blood Adv. 7, 4102–4106 (2023).

pubmed: 37235557 pmcid: 10388722 doi: 10.1182/bloodadvances.2023009817

Hagiwara, K. et al. Dynamics of age- versus therapy-related clonal hematopoiesis in long-term survivors of pediatric cancer. Cancer Discov. 13, 844–857 (2023).

pubmed: 36751942 pmcid: 10070170 doi: 10.1158/2159-8290.CD-22-0956

Chan, H. T., Chin, Y. M., Nakamura, Y. & Low, S. K. Clonal hematopoiesis in liquid biopsy: from biological noise to valuable clinical implications. Cancers (Basel). 12, 2277 (2020).

Huang, F. et al. Chemotherapy-associated clonal hematopoiesis mutations should be taken seriously in plasma cell-free DNA KRAS/NRAS/BRAF genotyping for metastatic colorectal cancer. Clin. Biochem 92, 46–53 (2021).

pubmed: 33737000 doi: 10.1016/j.clinbiochem.2021.03.005

Leal, A. et al. White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer. Nat. Commun. 11, 525 (2020).

pubmed: 31988276 pmcid: 6985115 doi: 10.1038/s41467-020-14310-3

Chan, H. T. et al. Clinical significance of clonal hematopoiesis in the interpretation of blood liquid biopsy. Mol. Oncol. 14, 1719–1730 (2020).

pubmed: 32449983 pmcid: 7400786 doi: 10.1002/1878-0261.12727

Ococks, E. et al. Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling. Ann. Oncol. 32, 522–532 (2021).

pubmed: 33359547 doi: 10.1016/j.annonc.2020.12.010

Croitoru, V. M. et al. Clonal hematopoiesis and liquid biopsy in gastrointestinal cancers. Front Med. (Lausanne) 8, 772166 (2021).

pubmed: 35127745 doi: 10.3389/fmed.2021.772166

Greytak, S. R. et al. Harmonizing cell-free DNA collection and processing practices through evidence-based guidance. Clin. Cancer Res. 26, 3104–3109 (2020).

pubmed: 32122922 pmcid: 7334102 doi: 10.1158/1078-0432.CCR-19-3015

Almasi, M. et al. Biobanking - the first step to successful liquid biopsy experiments. Klin. Onkol. 30, 9–12 (2017).

pubmed: 28903566 doi: 10.14735/amko20172S9

Colomer, R. et al. Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement. EClinicalMedicine 60, 102029 (2023).

pubmed: 37304496 pmcid: 10248077 doi: 10.1016/j.eclinm.2023.102029

Anagnostou, V. & Velculescu, V. E. Pushing the boundaries of liquid biopsies for early precision intervention. Cancer Discov. 14, 615–619 (2024).

pubmed: 38571422 doi: 10.1158/2159-8290.CD-24-0037

European Union. Ethical considerations for clinical trials on medicinal products conducted with the paediatric population. Eur. J. Health Law 15, 223–250 (2008).

doi: 10.1163/157180908X333228

De Luca, G. & Dono, M. The opportunities and challenges of molecular tagging next-generation sequencing in liquid biopsy. Mol. Diagn. Ther. 25, 537–547 (2021).

pubmed: 34224097 doi: 10.1007/s40291-021-00542-6

Kobayashi, K. et al. Cell-free DNA oncogene copy number as a surrogate molecular biomarker in ALK/MYCN-coamplified neuroblastoma. J. Pediatr. Hematol. Oncol. 43, e165–e168 (2021).

pubmed: 32032241 doi: 10.1097/MPH.0000000000001720

Combaret, V. et al. Circulating MYCN DNA as a tumor-specific marker in neuroblastoma patients. Cancer Res. 62, 3646–3648 (2002).

pubmed: 12097268

Combaret, V., Bergeron, C., Noguera, R., Iacono, I. & Puisieux, A. Circulating MYCN DNA predicts MYCN-amplification in neuroblastoma. J. Clin. Oncol. 23, 8919–8920 (2005). author reply 8920.

pubmed: 16314658 doi: 10.1200/JCO.2005.04.0170

Ma, Y. et al. Detection of MYCN amplification in serum DNA using conventional polymerase chain reaction. J. Korean Med. Sci. 31, 1392–1396 (2016).

pubmed: 27510381 pmcid: 4974179 doi: 10.3346/jkms.2016.31.9.1392

Kojima, M. et al. Detection of MYCN amplification using blood plasma: noninvasive therapy evaluation and prediction of prognosis in neuroblastoma. Pediatr. Surg. Int 29, 1139–1145 (2013).

pubmed: 24022278 doi: 10.1007/s00383-013-3374-9

Panachan, J. et al. Extracellular Vesicle-Based Method for Detecting MYCN Amplification Status of Pediatric Neuroblastoma. Cancers (Basel) 14, 2627 (2022).

pubmed: 35681607 doi: 10.3390/cancers14112627

Chicard, M. et al. Genomic Copy Number Profiling Using Circulating Free Tumor DNA Highlights Heterogeneity in Neuroblastoma. Clin. Cancer Res 22, 5564–5573 (2016).

pubmed: 27440268 doi: 10.1158/1078-0432.CCR-16-0500

Combaret, V. et al. Influence of neuroblastoma stage on serum-based detection of MYCN amplification. Pediatr. Blood Cancer 53, 329–331 (2009).

pubmed: 19301388 pmcid: 2857568 doi: 10.1002/pbc.22009

Gotoh, T. et al. Prediction of MYCN amplification in neuroblastoma using serum DNA and real-time quantitative polymerase chain reaction. J. Clin. Oncol. 23, 5205–5210 (2005).

pubmed: 16051962 doi: 10.1200/JCO.2005.02.014

Iehara, T. et al. A prospective evaluation of liquid biopsy for detecting MYCN amplification in neuroblastoma patients. Jpn J. Clin. Oncol. 49, 743–748 (2019).

pubmed: 31053863 doi: 10.1093/jjco/hyz063

Yagyu, S. et al. Serum-based quantification of MYCN gene amplification in young patients with neuroblastoma: potential utility as a surrogate biomarker for neuroblastoma. PLoS One 11, e0161039 (2016).

pubmed: 27513929 pmcid: 4981470 doi: 10.1371/journal.pone.0161039

Van Roy, N. et al. Shallow whole genome sequencing on circulating cell-free DNA allows reliable noninvasive copy-number profiling in neuroblastoma patients. Clin. Cancer Res. 23, 6305–6314 (2017).

pubmed: 28710315 doi: 10.1158/1078-0432.CCR-17-0675

Lodrini, M. et al. Targeted analysis of cell-free circulating tumor DNA is suitable for early relapse and actionable target detection in patients with neuroblastoma. Clin. Cancer Res. 28, 1809–1820 (2022).

pubmed: 35247920 doi: 10.1158/1078-0432.CCR-21-3716

Lodrini, M. et al. Using droplet digital PCR to analyze MYCN and ALK copy number in plasma from patients with neuroblastoma. Oncotarget 8, 85234–85251 (2017).

pubmed: 29156716 pmcid: 5689606 doi: 10.18632/oncotarget.19076

Combaret, V. et al. Detection of tumor ALK status in neuroblastoma patients using peripheral blood. Cancer Med. 4, 540–550 (2015).

pubmed: 25653133 pmcid: 4402069 doi: 10.1002/cam4.414

Kahana-Edwin, S. et al. Neuroblastoma molecular risk-stratification of DNA copy number and ALK genotyping via cell-free circulating tumor DNA profiling. Cancers (Basel) 13, 3365 (2021).

pubmed: 34282791 doi: 10.3390/cancers13133365

Combaret, V. et al. Determination of 17q gain in patients with neuroblastoma by analysis of circulating DNA. Pediatr. Blood Cancer 56, 757–761 (2011).

pubmed: 21370407 doi: 10.1002/pbc.22816

Yagyu, S. et al. Preoperative analysis of 11q loss using circulating tumor-released DNA in serum: a novel diagnostic tool for therapy stratification of neuroblastoma. Cancer Lett. 309, 185–189 (2011).

pubmed: 21726937 doi: 10.1016/j.canlet.2011.05.032

Applebaum, M. A. et al. 5-Hydroxymethylcytosine profiles in circulating cell-free DNA associate with disease burden in children with neuroblastoma. Clin. Cancer Res. 26, 1309–1317 (2020).

pubmed: 31852832 doi: 10.1158/1078-0432.CCR-19-2829

Lodrini, M. et al. Circulating cell-free DNA assessment in biofluids from children with neuroblastoma demonstrates feasibility and potential for minimally invasive molecular diagnostics. Cancers (Basel) 14, 2080 (2022).

pubmed: 35565208 doi: 10.3390/cancers14092080

Stutterheim, J. et al. The prognostic value of fast molecular response of marrow disease in patients aged over 1 year with stage 4 neuroblastoma. Eur. J. Cancer 47, 1193–1202 (2011).

pubmed: 21429738 doi: 10.1016/j.ejca.2011.02.003

Cimmino, F., Lasorsa, V. A., Vetrella, S., Iolascon, A. & Capasso, M. A targeted gene panel for circulating tumor DNA sequencing in neuroblastoma. Front Oncol. 10, 596191 (2020).

pubmed: 33381456 pmcid: 7769379 doi: 10.3389/fonc.2020.596191

Riehl, L. et al. Targeted parallel DNA sequencing detects circulating tumor-associated variants of the mitochondrial and nuclear genomes in patients with neuroblastoma. Cancer Rep. (Hoboken) 6, e1687 (2023).

pubmed: 35899825 doi: 10.1002/cnr2.1687

Duan, C. et al. Whole exome sequencing reveals novel somatic alterations in neuroblastoma patients with chemotherapy. Cancer Cell Int. 18, 21 (2018).

pubmed: 29467591 pmcid: 5816515 doi: 10.1186/s12935-018-0521-3

van Wezel, E. M. et al. Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma. J. Mol. Diagn. 17, 43–52 (2015).

pubmed: 25445214 doi: 10.1016/j.jmoldx.2014.09.005

Su, Y. et al. Dynamic alterations of plasma cell free DNA in response to chemotherapy in children with neuroblastoma. Cancer Med. 8, 1558–1566 (2019).

pubmed: 30793512 pmcid: 6488154 doi: 10.1002/cam4.2045

van Zogchel, L. M. J. et al. Hypermethylated RASSF1A as circulating tumor DNA marker for disease monitoring in neuroblastoma. JCO Precis Oncol. 4, PO.19.00261 (2020).

pubmed: 32923888 pmcid: 7446415

Su, Y. et al. Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma. BMC Cancer 20, 102 (2020).

pubmed: 32028911 pmcid: 7006086 doi: 10.1186/s12885-020-6562-8

Wang, X. et al. Plasma cell-free DNA quantification is highly correlated to tumor burden in children with neuroblastoma. Cancer Med 7, 3022–3030 (2018).

pubmed: 29905010 pmcid: 6051223 doi: 10.1002/cam4.1586

Sausen, M. et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nat. Genet 45, 12–17 (2013).

pubmed: 23202128 doi: 10.1038/ng.2493

Yagyu, S. et al. Circulating methylated-DCR2 gene in serum as an indicator of prognosis and therapeutic efficacy in patients with MYCN nonamplified neuroblastoma. Clin. Cancer Res. 14, 7011–7019 (2008).

pubmed: 18980997 doi: 10.1158/1078-0432.CCR-08-1249

Misawa, A. et al. RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a prognostic marker. Br. J. Cancer 100, 399–404 (2009).

pubmed: 19165202 pmcid: 2634715 doi: 10.1038/sj.bjc.6604887

Charlton, J. et al. Methylome analysis identifies a Wilms tumor epigenetic biomarker detectable in blood. Genome Biol. 15, 434 (2014).

pubmed: 25134821 pmcid: 4310621 doi: 10.1186/s13059-014-0434-y

Ueno-Yokohata, H. et al. Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA. Genes Chromosomes Cancer 57, 525–529 (2018).

pubmed: 30126017 doi: 10.1002/gcc.22648

Biderman Waberski, M. et al. Urine cell-free DNA is a biomarker for nephroblastomatosis or Wilms tumor in PIK3CA-related overgrowth spectrum (PROS). Genet Med 20, 1077–1081 (2018).

pubmed: 29300373 doi: 10.1038/gim.2017.228

Treger, T. D. et al. Somatic TP53 mutations are detectable in circulating tumor DNA from children with anaplastic Wilms tumors. Transl. Oncol. 11, 1301–1306 (2018).

pubmed: 30172241 pmcid: 6121832 doi: 10.1016/j.tranon.2018.08.006

Chen, J. et al. Design of a targeted sequencing assay to detect rare mutations in circulating tumor DNA. Genet Test. Mol. Biomark. 23, 264–269 (2019).

doi: 10.1089/gtmb.2018.0173

Rossi, E. et al. Liquid biopsy in pediatric renal cancer: stage I and stage IV cases compared. Diagnostics (Basel) 10, 810 (2020).

Li, H. et al. Detection of circulating tumor cells from cryopreserved human sarcoma peripheral blood mononuclear cells. Cancer Lett. 403, 216–223 (2017).

pubmed: 28652021 pmcid: 5546157 doi: 10.1016/j.canlet.2017.05.032

Sittiju, P. et al. Osteosarcoma-specific genes as a diagnostic tool and clinical predictor of tumor progression. Biology (Basel) 11 (2022).

Batth, I. S. et al. Rare osteosarcoma cell subpopulation protein array and profiling using imaging mass cytometry and bioinformatics analysis. BMC Cancer 20, 715 (2020).

pubmed: 32736533 pmcid: 7395380 doi: 10.1186/s12885-020-07203-7

Satelli, A. et al. Universal marker and detection tool for human sarcoma circulating tumor cells. Cancer Res. 74, 1645–1650 (2014).

pubmed: 24448245 pmcid: 3959622 doi: 10.1158/0008-5472.CAN-13-1739

Fasanya, H. O., Dopico, P. J., Yeager, Z., Fan, Z. H. & Siemann, D. W. Using a combination of gangliosides and cell surface vimentin as surface biomarkers for isolating osteosarcoma cells in microfluidic devices. J. Bone Oncol. 28, 100357 (2021).

pubmed: 33912384 pmcid: 8065304 doi: 10.1016/j.jbo.2021.100357

Li, X. et al. [Expressions of ERCC2 and ERCC4 genes in osteosarcoma and peripheral blood lymphocytes and their clinical significance]. Beijing Da Xue Xue Bao Yi Xue Ban. 39, 467–471 (2007).

pubmed: 17940561

Wong, I. H., Chan, A. T. & Johnson, P. J. Quantitative analysis of circulating tumor cells in peripheral blood of osteosarcoma patients using osteoblast-specific messenger RNA markers: a pilot study. Clin. Cancer Res. 6, 2183–2188, (2000).

pubmed: 10873067

Luo, Z., Liu, M., Zhang, H. & Xia, Y. Association of circulating miR-125b and survival in patients with osteosarcoma-A single center experience. J. Bone Oncol. 5, 167–172 (2016).

pubmed: 28008378 pmcid: 5154701 doi: 10.1016/j.jbo.2016.06.002

Nakka, M. et al. Biomarker significance of plasma and tumor miR-21, miR-221, and miR-106a in osteosarcoma. Oncotarget 8, 96738–96752 (2017).

pubmed: 29228567 pmcid: 5722519 doi: 10.18632/oncotarget.18236

Tian, Q. et al. A causal role for circulating miR-34b in osteosarcoma. Eur. J. Surg. Oncol. 40, 67–72 (2014).

pubmed: 24063968 doi: 10.1016/j.ejso.2013.08.024

Zhu, K. et al. Circular RNA hsa_circ_0000885 levels are increased in tissue and serum samples from patients with osteosarcoma. Med. Sci. Monit. 25, 1499–1505 (2019).

pubmed: 30802235 pmcid: 6400018 doi: 10.12659/MSM.914899

Ma, W. et al. Circulating miR-148a is a significant diagnostic and prognostic biomarker for patients with osteosarcoma. Tumour Biol. 35, 12467–12472 (2014).

pubmed: 25185654 doi: 10.1007/s13277-014-2565-x

Monterde-Cruz, L. et al. Circulating miR-215-5p and miR-642a-5p as potential biomarker for diagnosis of osteosarcoma in Mexican population. Hum. Cell 31, 292–299 (2018).

pubmed: 29907935 doi: 10.1007/s13577-018-0214-1

Fujiwara, T. et al. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma. Oncotarget 8, 33375–33392 (2017).

pubmed: 28380419 pmcid: 5464875 doi: 10.18632/oncotarget.16498

Zhang, C., Yao, C., Li, H., Wang, G. & He, X. Combined elevation of microRNA-196a and microRNA-196b in sera predicts unfavorable prognosis in patients with osteosarcomas. Int. J. Mol. Sci. 15, 6544–6555 (2014).

pubmed: 24747591 pmcid: 4013646 doi: 10.3390/ijms15046544

Kohama, I. et al. Comprehensive serum and tissue microRNA profiling in dedifferentiated liposarcoma. Oncol. Lett. 22, 623 (2021).

pubmed: 34285721 pmcid: 8258628 doi: 10.3892/ol.2021.12884

Allen-Rhoades, W. et al. Cross-species identification of a plasma microRNA signature for detection, therapeutic monitoring, and prognosis in osteosarcoma. Cancer Med. 4, 977–988 (2015).

pubmed: 25784290 pmcid: 4529336 doi: 10.1002/cam4.438

Yao, Z. S. et al. Diagnostic and prognostic implications of serum miR-101 in osteosarcoma. Cancer Biomark. 22, 127–133 (2018).

pubmed: 29630525 pmcid: 6004928 doi: 10.3233/CBM-171103

Tang, J., Zhao, H., Cai, H. & Wu, H. Diagnostic and prognostic potentials of microRNA-27a in osteosarcoma. Biomed. Pharmacother. 71, 222–226 (2015).

pubmed: 25960240 doi: 10.1016/j.biopha.2015.01.025

Zhou, L. et al. The diagnostic effect of serum miR-139-5p as an indicator in osteosarcoma. Cancer Biomark. 23, 561–567 (2018).

pubmed: 30347602 doi: 10.3233/CBM-181744

Wang, N. G., Wang, D. C., Tan, B. Y., Wang, F. & Yuan, Z. N. Down-regulation of microRNA152 is associated with the diagnosis and prognosis of patients with osteosarcoma. Int. J. Clin. Exp. Pathol. 8, 9314–9319 (2015).

pubmed: 26464682 pmcid: 4583914

Zhao, X. et al. Downregulation of microRNA-95-3p suppresses cell growth of osteosarcoma via CDKN1A/p21 expression. Oncol. Rep. 39, 289–297 (2018).

pubmed: 29115549

Wang, L., Gao, H., Gong, N. & Gong, M. Downregulation of microRNA-497 is associated with upregulation of synuclein γ in patients with osteosarcoma. Exp. Ther. Med 12, 3761–3766 (2016).

pubmed: 28105108 pmcid: 5228581 doi: 10.3892/etm.2016.3838

Shi, L., Xie, C., Zhu, J. & Chen, X. Downregulation of serum miR-194 predicts poor prognosis in osteosarcoma patients. Ann. Diagn. Pathol. 46, 151488 (2020).

pubmed: 32172218 doi: 10.1016/j.anndiagpath.2020.151488

Gong, L. et al. Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1. Biochem. Biophys. Res. Commun. 500, 170–176 (2018).

pubmed: 29626470 doi: 10.1016/j.bbrc.2018.04.016

Xu, J. F. et al. Exosomes containing differential expression of microRNA and mRNA in osteosarcoma that can predict response to chemotherapy. Oncotarget 8, 75968–75978 (2017).

pubmed: 29100284 pmcid: 5652678 doi: 10.18632/oncotarget.18373

Zhang, K. et al. Extracellular vesicle-mediated delivery of miR-101 inhibits lung metastasis in osteosarcoma. Theranostics 10, 411–425 (2020).

pubmed: 31903129 pmcid: 6929625 doi: 10.7150/thno.33482

Huang, C. et al. A four serum-miRNA panel serves as a potential diagnostic biomarker of osteosarcoma. Int. J. Clin. Oncol. 24, 976–982 (2019).

pubmed: 31111286 doi: 10.1007/s10147-019-01433-x

Cuscino, N. et al. Gathering novel circulating exosomal microRNA in osteosarcoma cell lines and possible implications for the disease. Cancers (Basel) 11, 1924 (2019).

Lian, F., Cui, Y., Zhou, C., Gao, K. & Wu, L. Identification of a plasma four-microRNA panel as potential noninvasive biomarker for osteosarcoma. PLoS One 10, e0121499 (2015).

pubmed: 25775010 pmcid: 4361617 doi: 10.1371/journal.pone.0121499

Huang, C. et al. Identification of circulating miR-663a as a potential biomarker for diagnosing osteosarcoma. Pathol. Res Pract. 215, 152411 (2019).

pubmed: 30987831 doi: 10.1016/j.prp.2019.04.003

Zhou, G. et al. Identification of miR-199a-5p in serum as noninvasive biomarkers for detecting and monitoring osteosarcoma. Tumour Biol. 36, 8845–8852 (2015).

pubmed: 26069101 doi: 10.1007/s13277-015-3421-3

Xu, K. et al. Identification of potential micro-messenger RNAs (miRNA-mRNA) interaction network of osteosarcoma. Bioengineered 12, 3275–3293 (2021).

pubmed: 34252359 pmcid: 8806609 doi: 10.1080/21655979.2021.1947065

Yuan, J., Chen, L., Chen, X., Sun, W. & Zhou, X. Identification of serum microRNA-21 as a biomarker for chemosensitivity and prognosis in human osteosarcoma. J. Int. Med. Res 40, 2090–2097 (2012).

pubmed: 23321165 doi: 10.1177/030006051204000606

Cong, C. et al. Identification of serum miR-124 as a biomarker for diagnosis and prognosis in osteosarcoma. Cancer Biomark. 21, 449–454 (2018).

pubmed: 29125481 doi: 10.3233/CBM-170672

Xie, L. et al. Identification of the miRNA-mRNA regulatory network of small cell osteosarcoma based on RNA-seq. Oncotarget 8, 42525–42536 (2017).

pubmed: 28477009 pmcid: 5522085 doi: 10.18632/oncotarget.17208

Wang, T., Ji, F., Dai, Z., Xie, Y. & Yuan, D. Increased expression of microRNA-191 as a potential serum biomarker for diagnosis and prognosis in human osteosarcoma. Cancer Biomark. 15, 543–550 (2015).

pubmed: 26406942 doi: 10.3233/CBM-150493

Zhang, X. et al. Influence mechanism of miRNA-144 on proliferation and apoptosis of osteosarcoma cells. Oncol. Lett. 19, 1530–1536 (2020).

pubmed: 31966078

Li, H. et al. MicroRNA screening identifies circulating microRNAs as potential biomarkers for osteosarcoma. Oncol. Lett. 10, 1662–1668 (2015).

pubmed: 26622728 pmcid: 4533320 doi: 10.3892/ol.2015.3378

Tian, Z. G. et al. MicroRNA-337-5p participates in the development and progression of osteosarcoma via ERBB, MAPK and VEGF pathways. Eur. Rev. Med Pharm. Sci. 22, 5460–5470 (2018).

Liu, W., Zhao, X., Zhang, Y. J., Fang, G. W. & Xue, Y. MicroRNA-375 as a potential serum biomarker for the diagnosis, prognosis, and chemosensitivity prediction of osteosarcoma. J. Int. Med. Res. 46, 975–983 (2018).

pubmed: 29115164 doi: 10.1177/0300060517734114

Xu, N., Yang, W., Liu, Y., Yan, F. & Yu, Z. MicroRNA-411 promoted the osteosarcoma progression by suppressing MTSS1 expression. Environ. Sci. Pollut. Res. Int. 25, 12064–12071 (2018).

pubmed: 29453719 doi: 10.1007/s11356-018-1331-9

Zhou, X., Natino, D., Zhai, X., Gao, Z. & He, X. MicroRNA‑22 inhibits the proliferation and migration, and increases the cisplatin sensitivity, of osteosarcoma cells. Mol. Med. Rep. 17, 7209–7217 (2018).

pubmed: 29568877 pmcid: 5928679

Lian, H., Zhou, Y., Sun, Z. & Liu, K. MicroRNA34a is associated with chemotherapy resistance, metastasis, recurrence, survival, and prognosis in patient with osteosarcoma. Medicine (Baltimore) 101, e30722 (2022).

pubmed: 36197268 doi: 10.1097/MD.0000000000030722

Sun, Y., He, N., Dong, Y. & Jiang, C. MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma. Sci. Rep. 6, 34238 (2016).

pubmed: 27681638 pmcid: 5041092 doi: 10.1038/srep34238

Cao, L., Wang, J. & Wang, P. Q. MiR-326 is a diagnostic biomarker and regulates cell survival and apoptosis by targeting Bcl-2 in osteosarcoma. Biomed. Pharmacother. 84, 828–835 (2016).

pubmed: 27723574 doi: 10.1016/j.biopha.2016.10.008

Zhou, S. et al. miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma. Tumour Biol. 37, 9001–9007 (2016).

pubmed: 26758431 doi: 10.1007/s13277-015-4578-5

Wang, S. N. et al. miR-491 inhibits osteosarcoma lung metastasis and chemoresistance by targeting αB-crystallin. Mol. Ther. 25, 2140–2149 (2017).

pubmed: 28648665 pmcid: 5589150 doi: 10.1016/j.ymthe.2017.05.018

Pang, P. C., Shi, X. Y., Huang, W. L. & Sun, K. miR-497 as a potential serum biomarker for the diagnosis and prognosis of osteosarcoma. Eur. Rev. Med Pharm. Sci. 20, 3765–3769 (2016).

Liu, K., Sun, X., Zhang, Y., Liu, L. & Yuan, Q. MiR-598: a tumor suppressor with biomarker significance in osteosarcoma. Life Sci. 188, 141–148 (2017).

pubmed: 28882648 doi: 10.1016/j.lfs.2017.09.003

Lei, J. et al. miRNA identification by nuclease digestion in ELISA for diagnosis of osteosarcoma. Biotechnol. Appl. Biochem. 69, 1365–1372 (2022).

pubmed: 34081808 doi: 10.1002/bab.2209

Dong, J. et al. miRNA-223 is a potential diagnostic and prognostic marker for osteosarcoma. J. Bone Oncol. 5, 74–79 (2016).

pubmed: 27335775 pmcid: 4908189 doi: 10.1016/j.jbo.2016.05.001

Zhang, C., Yao, C., Li, H., Wang, G. & He, X. Serum levels of microRNA-133b and microRNA-206 expression predict prognosis in patients with osteosarcoma. Int. J. Clin. Exp. Pathol. 7, 4194–4203 (2014).

pubmed: 25120799 pmcid: 4129034

Li, S. et al. Serum microRNA-17 functions as a prognostic biomarker in osteosarcoma. Oncol. Lett. 12, 4905–4910 (2016).

pubmed: 28105199 pmcid: 5228414 doi: 10.3892/ol.2016.5362

Yang, Z. et al. Serum microRNA-221 functions as a potential diagnostic and prognostic marker for patients with osteosarcoma. Biomed. Pharmacother. 75, 153–158 (2015).

pubmed: 26422796 doi: 10.1016/j.biopha.2015.07.018

Fei, D. et al. Serum miR-9 as a prognostic biomarker in patients with osteosarcoma. J. Int. Med. Res. 42, 932–937 (2014).

pubmed: 24962996 doi: 10.1177/0300060514534643

Wang, T., Wu, J., Liu, X. & Li, S. Serum miR-34a is a potential diagnostic and prognostic marker for osteosarcoma. Int. J. Clin. Exp. Pathol. 10, 9683–9689 (2017).

pubmed: 31966849 pmcid: 6965930

Niu, J., Sun, Y., Guo, Q., Niu, D. & Liu, B. Serum miR-95-3p is a diagnostic and prognostic marker for osteosarcoma. Springerplus 5, 1947 (2016).

pubmed: 27917340 pmcid: 5102988 doi: 10.1186/s40064-016-3640-0

Cai, H., Zhao, H., Tang, J. & Wu, H. Serum miR-195 is a diagnostic and prognostic marker for osteosarcoma. J. Surg. Res. 194, 505–510 (2015).

pubmed: 25498513 doi: 10.1016/j.jss.2014.11.025

Liu, J. D. et al. Serum miR-300 as a diagnostic and prognostic biomarker in osteosarcoma. Oncol. Lett. 12, 3912–3918 (2016).

pubmed: 27895748 pmcid: 5104207 doi: 10.3892/ol.2016.5214

Li, Q., Song, S., Ni, G., Li, Y. & Wang, X. Serum miR-542-3p as a prognostic biomarker in osteosarcoma. Cancer Biomark. 21, 521–526 (2018).

pubmed: 29103020 doi: 10.3233/CBM-170255

Ouyang, L. et al. A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma. Med. Oncol. 30, 340 (2013).

pubmed: 23269581 doi: 10.1007/s12032-012-0340-7

Hua, Y., Jin, Z., Zhou, F., Zhang, Y. Q. & Zhuang, Y. The expression significance of serum MiR-21 in patients with osteosarcoma and its relationship with chemosensitivity. Eur. Rev. Med Pharm. Sci. 21, 2989–2994 (2017).

Hua, J. et al. Diagnostic and prognostic values of blood microRNA-Let7A for osteosarcoma. J. Bone Oncol. 12, 65–68 (2018).

pubmed: 29992090 pmcid: 6037640 doi: 10.1016/j.jbo.2018.05.001

Hong, Q., Fang, J., Pang, Y. & Zheng, J. Prognostic value of the microRNA-29 family in patients with primary osteosarcomas. Med. Oncol. 31, 37 (2014).

pubmed: 25015394 doi: 10.1007/s12032-014-0037-1

Wen, J. J., Ma, Y. D., Yang, G. S. & Wang, G. M. Analysis of circulating long non-coding RNA UCA1 as potential biomarkers for diagnosis and prognosis of osteosarcoma. Eur. Rev. Med. Pharm. Sci. 21, 498–503 (2017).

Xia, W. K. et al. Clinical implication of long noncoding RNA 91H expression profile in osteosarcoma patients. Onco Targets Ther. 9, 4645–4652 (2016).

pubmed: 27555785 pmcid: 4968861 doi: 10.2147/OTT.S103376

Chen, S., Liu, Z., Lu, S. & Hu, B. EPEL promotes the migration and invasion of osteosarcoma cells by upregulating ROCK1. Oncol. Lett. 17, 3133–3140 (2019).

pubmed: 30867743 pmcid: 6396117

Zhang, G. F., Zhou, B. S., An, X. C., An, F. M. & Li, S. H. LINC01278 is highly expressed in osteosarcoma and participates in the development of tumors by mediating the miR-134-5p/KRAS axis. Onco Targets Ther. 14, 683–695 (2021).

pubmed: 33531816 pmcid: 7847385 doi: 10.2147/OTT.S265591

Zhao, B., Liu, K. & Cai, L. LINK-A lncRNA functions in the metastasis of osteosarcoma by upregulating HIF1α. Oncol. Lett. 17, 5005–5011 (2019).

pubmed: 31186711 pmcid: 6507337

Wang, Y. et al. LncRNA FAL1 is a negative prognostic biomarker and exhibits pro-oncogenic function in osteosarcoma. J. Cell Biochem 119, 8481–8489 (2018).

pubmed: 29987852 doi: 10.1002/jcb.27074

Cai, L. et al. The lncRNA HNF1A-AS1 is a negative prognostic factor and promotes tumorigenesis in osteosarcoma. J. Cell Mol. Med. 21, 2654–2662 (2017).

pubmed: 28866868 pmcid: 5661255 doi: 10.1111/jcmm.12944

Sheng, K. & Li, Y. LncRNA TUG1 promotes the development of osteosarcoma through RUNX2. Exp. Ther. Med 18, 3002–3008 (2019).

pubmed: 31555384 pmcid: 6755426

Yang, Q., Yu, H., Yin, Q., Hu, X. & Zhang, C. lncRNA-NEF is downregulated in osteosarcoma and inhibits cancer cell migration and invasion by downregulating miRNA-21. Oncol. Lett. 17, 5403–5408 (2019).

pubmed: 31186758 pmcid: 6507433

Chen, S., Xu, X., Lu, S. & Hu, B. Long non-coding RNA HAND2-AS1 targets glucose metabolism and inhibits cancer cell proliferation in osteosarcoma. Oncol. Lett. 18, 1323–1329 (2019).

pubmed: 31423193 pmcid: 6607319

Han, F., Wang, C., Wang, Y. & Zhang, L. Long noncoding RNA ATB promotes osteosarcoma cell proliferation, migration and invasion by suppressing miR-200s. Am. J. Cancer Res. 7, 770–783 (2017).

pubmed: 28469952 pmcid: 5411787

Huo, Y. et al. MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2. Oncotarget 8, 46993–47006 (2017).

pubmed: 28388584 pmcid: 5564539 doi: 10.18632/oncotarget.16551

Song, Q. H. et al. Study on targeting relationship between miR-320b and FGD5-AS1 and its effect on biological function of osteosarcoma cells. Cancer Manag. Res. 12, 13589–13598 (2020).

pubmed: 33408528 pmcid: 7781231 doi: 10.2147/CMAR.S264682

Ma, B. et al. Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma. Tumour Biol. 37, 4445–4455 (2016).

pubmed: 26499949 doi: 10.1007/s13277-015-4301-6

Wang, J. et al. Circulating exosomal PD-L1 at initial diagnosis predicts outcome and survival of patients with osteosarcoma. Clin. Cancer Res. 29, 659–666 (2023).

pubmed: 36374561 doi: 10.1158/1078-0432.CCR-22-2682

Han, Z. et al. Integrated microfluidic-SERS for exosome biomarker profiling and osteosarcoma diagnosis. Biosens. Bioelectron. 217, 114709 (2022).

pubmed: 36115123 doi: 10.1016/j.bios.2022.114709

Han, Z. et al. Matrix-assisted laser desorption ionization mass spectrometry profiling of plasma exosomes evaluates osteosarcoma metastasis. iScience 24, 102906 (2021).

pubmed: 34401680 pmcid: 8355924 doi: 10.1016/j.isci.2021.102906

Han, Z. et al. SERS and MALDI-TOF MS based plasma exosome profiling for rapid detection of osteosarcoma. Analyst 146, 6496–6505 (2021).

pubmed: 34569564 doi: 10.1039/D1AN01163D

Thomson, B., Hawkins, D., Felgenhauer, J. & Radich, J. RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing’s sarcoma and alveolar rhabdomyosarcoma. Bone Marrow Transpl. 24, 527–533 (1999).

doi: 10.1038/sj.bmt.1701939

Yu, M., Wan, Y. F. & Zou, Q. H. Cell-free circulating mitochondrial DNA in the serum: a potential non-invasive biomarker for Ewing’s sarcoma. Arch. Med Res. 43, 389–394 (2012).

pubmed: 22728238 doi: 10.1016/j.arcmed.2012.06.007

Nie, C. L., Ren, W. H., Ma, Y., Xi, J. S. & Han, B. Circulating miR-125b as a biomarker of Ewing’s sarcoma in Chinese children. Genet Mol. Res. 14, 19049–19056 (2015).

pubmed: 26782555 doi: 10.4238/2015.December.29.12

Krumbholz, M. et al. Genomic EWSR1 fusion sequence as highly sensitive and dynamic plasma tumor marker in Ewing sarcoma. Clin. Cancer Res. 22, 4356–4365 (2016).

pubmed: 27283964 doi: 10.1158/1078-0432.CCR-15-3028

Hayashi, M. et al. Highly personalized detection of minimal Ewing sarcoma disease burden from plasma tumor DNA. Cancer 122, 3015–3023 (2016).

pubmed: 27351911 doi: 10.1002/cncr.30144

Lee, S. Y., Lim, S. & Cho, D. H. Personalized genomic analysis based on circulating tumor cells of extra-skeletal Ewing sarcoma of the uterus: a case report of a 16-year-old Korean female. Exp. Ther. Med 16, 1343–1349 (2018).

pubmed: 30116384 pmcid: 6090316

Benini, S. et al. Detection of circulating tumor cells in liquid biopsy from Ewing sarcoma patients. Cancer Manag. Res. 10, 49–60 (2018).

pubmed: 29386915 pmcid: 5765973 doi: 10.2147/CMAR.S141623

Turaga, S. M. et al. Identification of small extracellular vesicle protein biomarkers for pediatric Ewing Sarcoma. Front Mol. Biosci. 10, 1138594 (2023).

pubmed: 37122563 pmcid: 10140755 doi: 10.3389/fmolb.2023.1138594

Miyachi, M. et al. Circulating muscle-specific microRNA, miR-206, as a potential diagnostic marker for rhabdomyosarcoma. Biochem Biophys. Res. Commun. 400, 89–93 (2010).

pubmed: 20696132 doi: 10.1016/j.bbrc.2010.08.015

Ghamloush, F. et al. The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486. Sci. Rep. 9, 14242 (2019).

pubmed: 31578374 pmcid: 6775163 doi: 10.1038/s41598-019-50592-4

Tombolan, L. et al. Circulating miR-26a as potential prognostic biomarkers in pediatric rhabdomyosarcoma. Front Genet 11, 606274 (2020).

pubmed: 33362864 pmcid: 7758343 doi: 10.3389/fgene.2020.606274

Li, X., Seebacher, N. A., Hornicek, F. J., Xiao, T. & Duan, Z. Application of liquid biopsy in bone and soft tissue sarcomas: present and future. Cancer Lett. 439, 66–77 (2018).

pubmed: 30223067 doi: 10.1016/j.canlet.2018.09.012

Murray, M. J., Nicholson, J. C. & Coleman, N. Biology of childhood germ cell tumours, focussing on the significance of microRNAs. Andrology 3, 129–139 (2015).

pubmed: 25303610 doi: 10.1111/andr.277

Takami, H. & Ichimura, K. Biomarkers for risk-based treatment modifications for CNS germ cell tumors: updates on biological underpinnings, clinical trials, and future directions. Front Oncol. 12, 982608 (2022).

pubmed: 36132131 pmcid: 9483213 doi: 10.3389/fonc.2022.982608

Fankhauser, C. D., Nuño, M. M., Murray, M. J., Frazier, L. & Bagrodia, A. Circulating MicroRNAs for detection of germ cell tumours: a narrative review. Eur. Urol. Focus 8, 660–662 (2022).

pubmed: 35537936 doi: 10.1016/j.euf.2022.04.008

Bottani, M., Banfi, G. & Lombardi, G. Circulating miRNAs as diagnostic and prognostic biomarkers in common solid tumors: focus on lung, breast, prostate cancers, and osteosarcoma. J. Clin. Med. 8, 1661 (2019).

Jezierska, M., Gawrychowska, A. & Stefanowicz, J. Diagnostic, prognostic and predictive markers in pediatric germ cell tumors-past, present and future. Diagnostics (Basel) 12, 278 (2022).

Perut, F., Roncuzzi, L. & Baldini, N. The emerging roles of extracellular vesicles in osteosarcoma. Front Oncol. 9, 1342 (2019).

pubmed: 31850225 pmcid: 6901498 doi: 10.3389/fonc.2019.01342

Lobo, J., Gillis, A. J. M., Jerónimo, C., Henrique, R. & Looijenga, L. H. J. Human germ cell tumors are developmental cancers: impact of epigenetics on pathobiology and clinic. Int. J. Mol. Sci. 20, 258 (2019).

Sasaki, R., Osaki, M. & Okada, F. MicroRNA-based diagnosis and treatment of metastatic human osteosarcoma. Cancers (Basel). 11, 553 (2019).

De Martino, M., Chieffi, P. & Esposito, F. miRNAs and biomarkers in testicular germ cell tumors: an update. Int. J. Mol. Sci. 22, 1380 (2021).

Chavarriaga, J. & Hamilton, R. J. miRNAs for testicular germ cell tumours: contemporary indications for diagnosis, surveillance and follow-up. Andrology 11, 628–633 (2023).

pubmed: 36373757 doi: 10.1111/andr.13337

Zeuschner, P., Linxweiler, J. & Junker, K. Non-coding RNAs as biomarkers in liquid biopsies with a special emphasis on extracellular vesicles in urological malignancies. Expert Rev. Mol. Diagn. 20, 151–167 (2020).

pubmed: 31499007 doi: 10.1080/14737159.2019.1665998

Lakpour, N. et al. Potential biomarkers for testicular germ cell tumour: Risk assessment, diagnostic, prognostic and monitoring of recurrence. Andrologia 53, e13998 (2021).

pubmed: 33534171 doi: 10.1111/and.13998

Looijenga, L. H. J., Kao, C. S. & Idrees, M. T. Predicting gonadal germ cell cancer in people with disorders of sex development; insights from developmental biology. Int. J. Mol. Sci. 20, 5017 (2019).

Murray, M. J., Huddart, R. A. & Coleman, N. The present and future of serum diagnostic tests for testicular germ cell tumours. Nat. Rev. Urol. 13, 715–725 (2016).

pubmed: 27754472 doi: 10.1038/nrurol.2016.170

Ditonno, F. et al. The role of miRNA in testicular cancer: current insights and future perspectives. Medicina (Kaunas) 59, 2033 (2023).

Shulman, D. S. & Crompton, B. D. Using liquid biopsy in the treatment of patient with OS. Adv. Exp. Med Biol. 1257, 95–105 (2020).

pubmed: 32483734 doi: 10.1007/978-3-030-43032-0_9

A comprehensive overview of liquid biopsy applications in pediatric solid tumors.

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Auteurs

Ferdinand W Janssen (FW)

Nathalie S M Lak (NSM)

Claudia Y Janda (CY)

Lennart A Kester (LA)

Michael T Meister (MT)

Johannes H M Merks (JHM)

Marry M van den Heuvel-Eibrink (MM)

Max M van Noesel (MM)

Jozsef Zsiros (J)

Godelieve A M Tytgat (GAM)

Leendert H J Looijenga (LHJ)

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