Pan-cancer patterns of somatic copy number alteration

TLDR

Somatic copy number alterations (SCNAs) are key drivers of cancer, and understanding their role is a major research priority. The study analyzed SCNA patterns across 4,934 TCGA pan‑cancer samples. Whole‑genome doubling occurs in 37 % of tumors and is linked to higher SCNA rates, TP53 mutations, CCNE1 amplifications, and PPP2R alterations; internal SCNAs are shorter than telomere‑bounded ones; 140 recurrent focal SCNAs were identified, including 102 without known oncogene targets and 50 with mutated genes, with amplified non‑oncogene regions enriched for epigenetic regulators; and 7 % of region pairs were anticorrelated, often involving physically interacting proteins, underscoring diverse mechanisms and functional consequences of SCNAs.

Abstract

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.