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Rare Germline Copy Number Variations and Disease Susceptibility in Familial Melanoma.

About this Publication
Title
Rare Germline Copy Number Variations and Disease Susceptibility in Familial Melanoma.
Pubmed ID
27476724 (View this publication on the PubMed website)
Digital Object Identifier
Publication
J. Invest. Dermatol. 2016 Dec; Volume 136 (Issue 12): Pages 2436-2443
Authors
Shi J, Zhou W, Zhu B, Hyland PL, Bennett H, Xiao Y, Zhang X, Burke LS, Song L, Hsu CH, Yan C, Chen Q, Meerzaman D, Dagnall CL, Burdette L, Hicks B, Freedman ND, Chanock SJ, Yeager M, Tucker MA, ...show more Goldstein AM, Yang XR
Affiliations
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA.
  • Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA; Statistics Collaborative, Inc., Washington, DC, USA.
  • Computational Genomics Research Group, Center for Biomedical Informatics & Information Technology, National Cancer Institute, Bethesda, Maryland, USA.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA. Electronic address: royang@mail.nih.gov.
Abstract

Mounting evidence suggests that copy number variations (CNVs) can contribute to cancer susceptibility. The main goal of this study was to evaluate the role of germline CNVs in melanoma predisposition in high-risk melanoma families. We used genome-wide tiling comparative genomic hybridization and single nucleotide polymorphism arrays to characterize CNVs in 335 individuals (240 melanoma cases) from American melanoma-prone families (22 with germline CDKN2A or CDK4 mutations). We found that the global burden of overall CNVs (or deletions or duplications separately) was not significantly associated with case-control or CDKN2A/CDK4 mutation status after accounting for the familial dependence. However, we identified several rare CNVs that either involved known melanoma genes (e.g., PARP1, CDKN2A) or cosegregated with melanoma (duplication on 10q23.23, 3p12.2 and deletions on 8q424.3, 2q22.1) in families without mutations in known melanoma high-risk genes. Some of these CNVs were correlated with expression changes in disrupted genes based on RNASeq data from a subset of melanoma cases included in the CNV study. These results suggest that rare cosegregating CNVs may influence melanoma susceptibility in some melanoma-prone families and genes found in our study warrant further evaluation in future genetic analyses of melanoma.

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