A Pan-Cancer Compendium of Genes Deregulated by Somatic Genomic Rearrangement across More Than 1,400 Cases

Citation:

Zhang Y*, Yang L*, Kucherlapati M*, Chen F, Hadjipanayis A, Pantazi A, Bristow CA, Lee EA, .., Creighton CJ. A Pan-Cancer Compendium of Genes Deregulated by Somatic Genomic Rearrangement across More Than 1,400 Cases. Cell Reports 2018;10(24(2):515-527.

Abstract:

A systematic cataloguing of genes impacted by genomic rearrangement, using multiple patient cohorts and cancer types, can provide insight into cancer-relevant alterations outside of exome boundaries. By integrative analysis of whole genome sequencing (predominantly low pass) and gene expression data from 1448 cancers involving 18 histopathological types in The Cancer Genome Atlas, we identified hundreds of genes for which the nearby presence (within 100kb) of a somatic Structural Variant (SV) breakpoint was associated with altered expression. While genomic rearrangements were associated with widespread copy number alteration (CNA) patterns, approximately 1100 genes—including over-expressed cancer driver genes (e.g. TERT, ERBB2, CDK12, CDK4) and under-expressed tumor suppressors (e.g. TP53, RB1, PTEN, STK11)—showed SV-associated deregulation independent of CNA. SVs associated with disruption of topologically-associated domains, enhancer hijacking, or fusion transcripts were implicated in gene up-regulation patterns. For cancer-relevant pathways, SVs considerably extended upon how genes are impacted, beyond point mutation or CNA.

Last updated on 08/31/2018