Incorporation of somatic panels for the detection of haematopoietic transformation in children and young adults with leukaemia predisposition syndromes and with acquired cytopenias.
acute myeloid leukaemia
bone marrow failure
myelodysplastic syndromes
next generation sequencing
paediatric
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
25
09
2020
accepted:
25
11
2020
pubmed:
29
12
2020
medline:
28
9
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
Detection of somatic mutations may help verify the diagnosis of myelodysplastic syndrome (MDS) in patients with persistent cytopenias or with MDS-predisposition syndromes, prior to the development of overt leukemia. However, the spectrum and consequences of acquired changes in paediatric patients have not been fully evaluated, and especially not in the context of an underlying syndrome. We incorporated a targeted next-generation-sequencing panel of 54 genes for the detection of somatic mutations in paediatric and young adult patients with inherited or acquired cytopenias. Sixty-five patients were included in this study, of whom 17 (26%) had somatic mutations. We detected somatic mutations in 20% of individuals with inherited MDS-predisposition syndromes, including in patients with severe congenital neutropenia and Fanconi anaemia, and with germline mutations in SAMD9L. Thirty-eight per cent of children with acquired cytopenias and suspected MDS had somatic changes, most commonly in genes related to signal transduction and transcription. Molecularly abnormal clones often preceded cytogenetic changes. Thus, routine performance of somatic panels can establish the diagnosis of MDS and determine the optimal timing of haematopoietic stem cell transplantation, prior to the development of leukaemia. In addition, performing somatic panels in patients with inherited MDS-predisposition syndromes may reveal their unique spectrum of acquired mutations.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
570-580Informations de copyright
© 2020 British Society for Haematology and John Wiley & Sons Ltd.
Références
Baliakas P, Tesi B, Wartiovaara-Kautto U, Stray-Pedersen AR, Friis LS, Dybedal I, et al. Nordic Guidelines for germline predisposition to myeloid neoplasms in adults: recommendations for genetic diagnosis, clinical management and follow-up. Hemasphere. 2019;3(6):e321.
Davies SM. Monitoring and treatment of MDS in genetically susceptible persons. Hematology Am Soc Hematol Educ Program. 2019;2019(1):105-9.
Kennedy AL, Shimamura A. Genetic predisposition to MDS: clinical features and clonal evolution. Blood. 2019;133(10):1071-85.
Babushok DV, Bessler M, Olson TS. Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults. Leuk Lymphoma. 2016;57(3):520-36.
Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28(2):241-7.
Schwartz JR, Ma J, Lamprecht T, Walsh M, Wang S, Bryant V, et al. The genomic landscape of pediatric myelodysplastic syndromes. Nat Commun. 2017;8(1):1557.
Hirabayashi S, Flotho C, Moetter J, Heuser M, Hasle H, Gruhn B, et al. Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML. Blood. 2012;119(11):e96-e99.
Sakaguchi H, Makishima H, Muramatsu H, Visconte V, Jerez A, Jankowska AM, et al. Mutational analysis of RNA splicing machinery components in 206 children with myeloid malignancies. Leuk Res. 2012;36(12):e215-e217.
Obenauer JC, Kavelaars FG, Sanders MA, Hoogenboezem RM, de Vries AC, van Strien PM, et al. Lack of splice factor and cohesin complex mutations in pediatric myelodysplastic syndrome. Haematologica. 2016;101(12):e479-e481.
Pastor V, Hirabayashi S, Karow A, Wehrle J, Kozyra EJ, Nienhold R, et al. Mutational landscape in children with myelodysplastic syndromes is distinct from adults: specific somatic drivers and novel germline variants. Leukemia. 2017;31(3):759-62.
Hasle H. Myelodysplastic and myeloproliferative disorders of childhood. Hematology Am Soc Hematol Educ Program. 2016;2016(1):598-604.
Austin KM, Leary RJ, Shimamura A. The Shwachman-Diamond SBDS protein localizes to the nucleolus. Blood. 2005;106(4):1253-8.
Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19(1):4-23.
Stark B, Jeison M, Gabay LG, Mardoukh J, Luria D, Bar-Am I, et al. Classical and molecular cytogenetic abnormalities and outcome of childhood acute myeloid leukaemia: report from a referral centre in Israel. Br J Haematol. 2004;126(3):320-37.
Jiang L, Luo Y, Zhu S, Wang L, Ma L, Zhang H, et al. Mutation status and burden can improve prognostic prediction of patients with lower-risk myelodysplastic syndromes. Cancer Sci. 2020;111(2):580-91.
Dong F, Brynes RK, Tidow N, Welte K, Löwenberg B, Touw IP. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia. N Engl J Med. 1995;333(8):487-93.
Klimiankou M, Uenalan M, Kandabarau S, Nustede R, Steiert I, Mellor-Heineke S, et al. Ultra-sensitive CSF3R deep sequencing in patients with severe congenital neutropenia. Front Immunol. 2019;10:116.
Beekman R, Valkhof MG, Sanders MA, van Strien PM, Haanstra JR, Broeders L, et al. Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia. Blood. 2012;119(22):5071-7.
Skokowa J, Steinemann D, Katsman-Kuipers JE, Zeidler C, Klimenkova O, Klimiankou M, et al. Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis. Blood. 2014;123(14):2229-37.
Skokowa J, Dale DC, Touw IP, Zeidler C, Welte K. Severe congenital neutropenias. Nat Rev Dis Primers. 2017;3:17032.
Savage SA, Walsh MF. Myelodysplastic syndrome, acute myeloid leukemia, and cancer surveillance in fanconi anemia. Hematol Oncol Clin North Am. 2018;32(4):657-68.
Quentin S, Cuccuini W, Ceccaldi R, Nibourel O, Pondarre C, Pagès MP, et al. Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions. Blood. 2011;117(15):e161-e170.
Heidemann S, Bursic B, Zandi S, Li H, Abelson S, Klaassen RJ, et al. Cellular and molecular architecture of hematopoietic stem cells and progenitors in genetic models of bone marrow failure. JCI Insight. 2020;5(4):e131018.
Pastor VB, Sahoo SS, Boklan J, Schwabe GC, Saribeyoglu E, Strahm B, et al. Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. Haematologica. 2018;103(3):427-37.
Chen DH, Below JE, Shimamura A, Keel SB, Matsushita M, Wolff J, et al. Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L. Am J Hum Genet. 2016;98(6):1146-58.
Narumi S, Amano N, Ishii T, Katsumata N, Muroya K, Adachi M, et al. SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. Nat Genet. 2016;48(7):792-7.
Bono E, McLornan D, Travaglino E, Gandhi S, Gallì A, Khan AA, et al. Clinical, histopathological and molecular characterization of hypoplastic myelodysplastic syndrome. Leukemia. 2019;33(10):2495-505.
Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496-506.
Cabezón M, Bargay J, Xicoy B, García O, Borrás J, Tormo M, et al. Impact of mutational studies on the diagnosis and the outcome of high-risk myelodysplastic syndromes and secondary acute myeloid leukemia patients treated with 5-azacytidine. Oncotarget. 2018;9(27):19342-55.
Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet. 2003;34(2):148-50.
Loh ML, Vattikuti S, Schubbert S, Reynolds MG, Carlson E, Lieuw KH, et al. Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. Blood. 2004;103(6):2325-31.
Loh ML, Martinelli S, Cordeddu V, Reynolds MG, Vattikuti S, Lee CM, et al. Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Res. 2005;29(4):459-62.
Hof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE. Crystal structure of the tyrosine phosphatase SHP-2. Cell. 1998;92(4):441-50.
Yoshida R, Hasegawa T, Hasegawa Y, Nagai T, Kinoshita E, Tanaka Y, et al. Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. J Clin Endocrinol Metab. 2004;89(7):3359-64.
Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, et al. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am J Hum Genet. 2006;78(2):279-90.
Singhal D, Wee LYA, Kutyna MM, Chhetri R, Geoghegan J, Schreiber AW, et al. The mutational burden of therapy-related myeloid neoplasms is similar to primary myelodysplastic syndrome but has a distinctive distribution. Leukemia. 2019;33(12):2842-53.
Shukla GC, Singh J. Mutations of RNA splicing factors in hematological malignancies. Cancer Lett. 2017;409:1-8.
Shingai N, Harada Y, Iizuka H, Ogata Y, Doki N, Ohashi K, et al. Impact of splicing factor mutations on clinical features in patients with myelodysplastic syndromes. Int J Hematol. 2018;108(6):598-606.
Kawata E, Lazo-Langner A, Xenocostas A, Hsia CC, Howson-Jan K, Deotare U, et al. Clinical value of next-generation sequencing compared to cytogenetics in patients with suspected myelodysplastic syndrome. Br J Haematol. 2020. https://doi.org/10.1111/bjh.16891
Hong M, He G. The 2016 revision to the World Health Organization classification of myelodysplastic syndromes. J Transl Int Med. 2017;5(3):139-43.
Xia J, Miller CA, Baty J, Ramesh A, Jotte MRM, Fulton RS, et al. Somatic mutations and clonal hematopoiesis in congenital neutropenia. Blood. 2018;131(4):408-16.
Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616-27; quiz 99.
Metzeler KH, Herold T, Rothenberg-Thurley M, Amler S, Sauerland MC, Görlich D, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128(5):686-98.
Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23(6):703-13.
Dong F, Dale DC, Bonilla MA, Freedman M, Fasth A, Neijens HJ, et al. Mutations in the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. Leukemia. 1997;11(1):120-5.
Ma X, Liu Y, Liu Y, Alexandrov LB, Edmonson MN, Gawad C, et al. Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Nature. 2018;555(7696):371-6.
Wong TN, Miller CA, Jotte MRM, Bagegni N, Baty JD, Schmidt AP, et al. Cellular stressors contribute to the expansion of hematopoietic clones of varying leukemic potential. Nat Commun. 2018;9(1):455.
Gröschel S, Sanders MA, Hoogenboezem R, Zeilemaker A, Havermans M, Erpelinck C, et al. Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood. 2015;125(1):133-9.
Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209-21.
Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet. 2014;46(5):444-50.
Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017;49(8):1211-8.
Cheah JJC, Brown AL, Schreiber AW, Feng J, Babic M, Moore S, et al. A novel germline SAMD9L mutation in a family with ataxia-pancytopenia syndrome and pediatric acute lymphoblastic leukemia. Haematologica. 2019;104(7):e318-e321.
Garg M, Nagata Y, Kanojia D, Mayakonda A, Yoshida K, Haridas Keloth S, et al. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse. Blood. 2015;126(22):2491-501.