PT  - JOURNAL ARTICLE
AU  - Yiqun Zhang
AU  - Fengju Chen
AU  - Nuno A. Fonseca
AU  - Yao He
AU  - Masashi Fujita
AU  - Hidewaki Nakagawa
AU  - Zemin Zhang
AU  - Alvis Brazma
AU  - Chad J. Creighton
AU  - on behalf of the PCAWG Transcriptome Working Group, PCAWG Structural Variation Working Group
AU  - ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
TI  - Whole genome and RNA sequencing of 1,220 cancers reveals hundreds of genes deregulated by rearrangement of cis-regulatory elements
AID  - 10.1101/099861
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 099861
4099  - http://biorxiv.org/content/early/2017/11/28/099861.short
4100  - http://biorxiv.org/content/early/2017/11/28/099861.full
AB  - Using a dataset of somatic Structural Variants (SVs) in cancers from 2658 patients—1220 with corresponding gene expression data—we identified hundreds of genes for which the nearby presence (within 100kb) of an SV breakpoint was associated with altered expression. For the vast majority of these genes, expression was increased rather than decreased with corresponding SV event. Well-known up-regulated cancer-associated genes impacted by this phenomenon included TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. SVs upstream of TERT involved ~3% of cancer cases and were most frequent in liver-biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involved ~1% of non-amplified cases. For many genes, SVs were significantly associated with either increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the gene promoter was often increased with nearby SV breakpoint, which may involve inactivation of repressor elements.PCAWGthe Pan-Cancer Analysis of Whole Genomes projectSVStructural Variant