Genomic coamplification of CDK4/MDM2/FRS2 is associated with very poor prognosis and atypical clinical features in neuroblastoma patients.
Adaptor Proteins, Signal Transducing
/ genetics
Biomarkers, Tumor
/ genetics
Child
Chromosomes, Human, Pair 12
Comparative Genomic Hybridization
/ methods
Cyclin-Dependent Kinase 4
/ genetics
Gene Amplification
Humans
Membrane Proteins
/ genetics
Neuroblastoma
/ genetics
Prognosis
Proto-Oncogene Proteins c-mdm2
/ genetics
Retrospective Studies
Survival Rate
Exome Sequencing
/ methods
FRS2 gene
12q genomic amplification
atypical clinical features
neuroblastoma
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
24
07
2019
revised:
20
11
2019
accepted:
20
11
2019
pubmed:
23
11
2019
medline:
28
10
2020
entrez:
23
11
2019
Statut:
ppublish
Résumé
Neuroblastoma (NB) is the most common extracranial malignant tumor of childhood and is characterized by a broad heterogeneity in clinical presentation and evolution. Recent advances in pangenomic analysis of NB have revealed different recurrent chromosomal aberrations. Indeed, it is now well established that the overall genomic profile is important for treatment stratification. In previous studies, 11 genes were shown to be recurrently amplified (ODC1, ALK, GREB1, NTSR2, LIN28B, MDM2, CDK4, MYEOV, CCND1, TERT, and MYC) besides MYCN, with poor survival of NB patients harboring these amplifications being suggested. Genomic profiles of 628 NB samples analyzed by array-comparative genome hybridization (a-CGH) were re-examined to identify gene amplifications other them MYCN amplification. Clinical data were retrospectively collected. We additionally evaluated the association of FRS2 gene expression with NB patient outcome using the public R2 Platform. We found eight NB samples with high grade amplification of one or two loci on chromosome arm 12q. The regional amplifications were located on bands 12q13.3-q14.1 and 12q15-q21.1 involving the genes CDK4, MDM2, and the potential oncogenic gene FRS2. The CDK4, MDM2, and FRS2 loci were coamplified in 8/8 samples. The 12q amplifications were associated with very poor prognosis and atypical clinical features of NB patients. Further functional and clinical investigations are needed to confirm or refute these associations.
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Biomarkers, Tumor
0
FRS2 protein, human
0
Membrane Proteins
0
MDM2 protein, human
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
CDK4 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 4
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
277-285Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
Cheung NK, Dyer MA. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer. 2013;13:397-411.
Louis CU, Shohet JM. Neuroblastoma: molecular pathogenesis and therapy. Annu Rev Med. 2015;66:49-63.
Cheung NK, Zhang J, Lu C, et al. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA. 2012;307:1062-1071.
Janoueix-Lerosey I, Schleiermacher G, Michels E, et al. Overall genomic pattern is a predictor of outcome in neuroblastoma. J Clin Oncol. 2009;27:1026-1033.
Matthay KK, Maris JM, Schleiermacher G, et al. Neuroblastoma. Nat Rev Dis Primers. 2016;2:16078.
Schleiermacher G, Janoueix-Lerosey I, Ribeiro A, et al. Accumulation of segmental alterations determines progression in neuroblastoma. J Clin Oncol. 2010;28:3122-3130.
Carr J, Bown NP, Case MC, Hall AG, Lunec J, Tweddle DA. High-resolution analysis of allelic imbalance in neuroblastoma cell lines by single nucleotide polymorphism arrays. Cancer Genet Cytogenet. 2007;172:127-138.
Corvi R, Savelyeva L, Breit S, et al. Nonsyntenic amplification of MDM2 and MYCN in human neuroblastoma. Oncogene. 1995;10:1081-1086.
Fix A, Lucchesi C, Ribeiro A, et al. Characterization of amplicons in neuroblastoma: high-resolution mapping using DNA microarrays, relationship with outcome, and identification of overexpressed genes. Genes Chromosomes Cancer. 2008;47:819-834.
Fix A, Peter M, Pierron G, Aurias A, Delattre O, Janoueix-Lerosey I. High-resolution mapping of amplicons of the short arm of chromosome 1 in two neuroblastoma tumors by microarray-based comparative genomic hybridization. Genes Chromosomes Cancer. 2004;40:266-270.
Molenaar JJ, van Sluis P, Boon K, Versteeg R, Caron HN. Rearrangements and increased expression of cyclin D1 (CCND1) in neuroblastoma. Genes Chromosomes Cancer. 2003;36:242-249.
Su WT, Alaminos M, Mora J, Cheung NK, la Quaglia MP, Gerald WL. Positional gene expression analysis identifies 12q overexpression and amplification in a subset of neuroblastomas. Cancer Genet Cytogenet. 2004;154:131-137.
Guimier A, Ferrand S, Pierron G, et al. Clinical characteristics and outcome of patients with neuroblastoma presenting genomic amplification of loci other than MYCN. PLoS One. 2014;9:e101990.
Depuydt P, Boeva V, Hocking TD, et al. Genomic amplifications and distal 6q loss: novel markers for poor survival in high-risk neuroblastoma patients. J Natl Cancer Inst. 2018;110:1084-1093.
Tweddle DA, Pearson ADJ, Haber M, et al. The p53 pathway and its inactivation in neuroblastoma. Cancer Lett. 2003;197:93-98.
Carr-Wilkinson J, O'Toole K, Wood KM, et al. High frequency of p53/MDM2/p14ARF pathway abnormalities in relapsed neuroblastoma. Clin Cancer Res. 2010;16:1108-1118.
Chen Z, Lin Y, Barbieri E, et al. Mdm2 deficiency suppresses MYCN-driven neuroblastoma tumorigenesis in vivo. Neoplasia. 2009;11:753-762.
Rihani A, Vandesompele J, Speleman F, van Maerken T. Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma. Cancer Cell Int. 2015;15:76.
Molenaar JJ, Ebus ME, Koster J, et al. Cyclin D1 and CDK4 activity contribute to the undifferentiated phenotype in neuroblastoma. Cancer Res. 2008;68:2599-2609.
Gotoh N. Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins. Cancer Sci. 2008;99:1319-1325.
Delpuech O, Rooney C, Mooney L, et al. Identification of pharmacodynamic transcript biomarkers in response to FGFR inhibition by AZD4547. Mol Cancer Ther. 2016;15:2802-2813.
Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10:116-129.
Jing W, Lan T, Chen H, et al. Amplification of FRS2 in atypical lipomatous tumour/well-differentiated liposarcoma and de-differentiated liposarcoma: a clinicopathological and genetic study of 146 cases. Histopathology. 2018;72:1145-1155.
He X, Pang Z, Zhang X, et al. Consistent amplification of FRS2 and MDM2 in low-grade osteosarcoma: a genetic study of 22 cases with clinicopathologic analysis. Am J Surg Pathol. 2018;42:1143-1155.
Ranzi V, Meakin SO, Miranda C, Mondellini P, Pierotti MA, Greco A. The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK oncoproteins. Endocrinology. 2003;144:922-928.
Zhang Y, Zhang J, Lin Y, et al. Role of epithelial cell fibroblast growth factor receptor substrate 2alpha in prostate development, regeneration and tumorigenesis. Development. 2008;135:775-784.
Luo LY, Kim E, Cheung HW, et al. The tyrosine kinase adaptor protein FRS2 is oncogenic and amplified in high-grade serous ovarian cancer. Mol Cancer Res. 2015;13:502-509.
Park JR, Bagatell R, Cohn SL, et al. Revisions to the international neuroblastoma response criteria: a consensus statement from the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol. 2017;35:2580-2587.
Pezzolo A, Sementa AR, Lerone M, et al. Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma. Cancer Biol Ther. 2017;18:285-289.
DePristo MA, Banks E, Poplin R, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011;43:491-498.
Kocak H, Ackermann S, Hero B, et al. Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma. Cell Death Dis. 2013;4:e586.
Grasso S, Cangelosi D, Chapelle J, et al. The SRCIN1/p140Cap adaptor protein negatively regulates the aggressiveness of neuroblastoma. Cell Death Differ. 2019 (in press).
Reva B, Antipin Y, Sander C. Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res. 2011;39(17):e118.
McClelland SE. Role of chromosomal instability in cancer progression. Endocr Relat Cancer. 2017;24:T23-T31.
Bakhoum SF, Compton DA. Chromosomal instability and cancer: a complex relationship with therapeutic potential. J Clin Investig. 2012;122:1138-1143.
Birkbak NJ, Eklund AC, Li Q, et al. Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res. 2011;71:3447-3452.
Wang XH, Wu HY, Gao J, Wang XH, Gao TH, Zhang SF. FGF represses metastasis of neuroblastoma regulated by MYCN and TGF-β1 induced LMO1 via control of let-7 expression. Brain Res. 2019;1704:219-228.
Oldridge DA, Truong B, Russ D, et al. Differences in genomic profiles and outcomes between thoracic and adrenal neuroblastoma. J Natl Cancer Inst. 2019;111:1192-1201.
Desai A, Adjei AA. FGFR signaling as a target for lung cancer therapy. J Thorac Oncol. 2016;11:9-20.
Yashiro M, Matsuoka T. Fibroblast growth factor receptor signaling as therapeutic targets in gastric cancer. World J Gastroenterol. 2016;22:2415-2423.
Zhou WY, Zheng H, Du XL, et al. Characterization of FGFR signaling pathway as therapeutic targets for sarcoma patients. Cancer Biol Med. 2016;13:260-268.
Hadari YR, Gotoh N, Kouhara H, Lax I, Schlessinger J. Critical role for the docking-protein FRS2 alpha in FGF receptor-mediated signal transduction pathways. Proc Natl Acad Sci USA. 2001;98:8578-8583.
Sato T, Gotoh N. The FRS2 family of docking/scaffolding adaptor proteins as therapeutic targets of cancer treatment. Expert Opin Ther Targets. 2009;13:689-700.
Touat M, Ileana E, Postel-Vinay S, Andre F, Soria JC. Targeting FGFR signaling in cancer. Clin Cancer Res. 2015;21:2684-2694.