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Nat Genet DOI:10.1038/ng.2760

Pan-cancer patterns of somatic copy number alteration.

Publication TypeJournal Article
Year of Publication2013
AuthorsZack, TI, Schumacher, SE, Carter, SL, Cherniack, AD, Saksena, G, Tabak, B, Lawrence, MS, Zhsng, C-Z, Wala, J, Mermel, CH, Sougnez, C, Gabriel, SB, Hernandez, B, Shen, H, Laird, PW, Getz, G, Meyerson, M, Beroukhim, R
JournalNat Genet
Date Published2013 Oct
KeywordsDNA Copy Number Variations, Epigenesis, Genetic, Gene Regulatory Networks, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Mutagenesis, Neoplasms, Ploidies

Determining how somatic copy number alterations (SCNAs) promote cancer is an important goal. We characterized SCNA patterns in 4,934 cancers from The Cancer Genome Atlas Pan-Cancer data set. Whole-genome doubling, observed in 37% of cancers, was associated with higher rates of every other type of SCNA, TP53 mutations, CCNE1 amplifications and alterations of the PPP2R complex. SCNAs that were internal to chromosomes tended to be shorter than telomere-bounded SCNAs, suggesting different mechanisms underlying their generation. Significantly recurrent focal SCNAs were observed in 140 regions, including 102 without known oncogene or tumor suppressor gene targets and 50 with significantly mutated genes. Amplified regions without known oncogenes were enriched for genes involved in epigenetic regulation. When levels of genomic disruption were accounted for, 7% of region pairs were anticorrelated, and these regions tended to encompass genes whose proteins physically interact, suggesting related functions. These results provide insights into mechanisms of generation and functional consequences of cancer-related SCNAs.


Alternate JournalNat. Genet.
PubMed ID24071852
PubMed Central IDPMC3966983
Grant ListU24 CA143882 / CA / NCI NIH HHS / United States
U54 CA143798 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24CA143882 / CA / NCI NIH HHS / United States
U54HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
T32 HG002295 / HG / NHGRI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
U24CA143867 / CA / NCI NIH HHS / United States
U24CA143845 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U54CA143798 / CA / NCI NIH HHS / United States