Pan-cancer patterns of somatic copy-number alteration

Determining how somatic copy-number alterations (SCNAs) promote cancer is an important goal. We characterized SCNA patterns among 4934 cancers from The Cancer Genome Atlas Pan-Cancer dataset. 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 of 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 are enriched for genes involved in epigenetic regulation. When levels of genomic disruption were accounted for, 7% of region pairs anticorrelated, and these tended to encompass genes whose proteins physically interact, suggesting related functions. These results provide insights into mechanisms of generation and functional consequences of cancer SCNAs.