Scientific Publications

Pan-cancer patterns of somatic copy number alteration.

Publication TypeJournal Article
AuthorsZack, TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G., Tabak B., Lawrence MS, Zhang CZ, Wala J., Mermel CH, Sougnez C., Gabriel SB, Hernandez B., Shen H., Laird PW, Getz G., Meyerson M., and Beroukhim R.
AbstractDetermining 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.
Year of Publication2013
JournalNature genetics
Volume45
Issue10
Pages1134-1140
Date Published (YYYY/MM/DD)2013/09/26
ISSN Number1061-4036
DOI10.1038/ng.2760
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24071852?dopt=Abstract