Zhang, YikunChen, FengjuFonseca, NunoHe, YaoFujita, MasashiNakagawa, HidewakiZhang, ZeminBrazma, AlvisPCAWG Transcriptome Working GroupPCAWG Structural Variation Working GroupCreighton, Chad J.PCAWG ConsortiumOssowski, Stephan2020-04-242020-04-242020Zhang Y, Chen F, Fonseca NA, He Y, Fujita M, Nakagawa H et al. High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations. Nat Commun. 2020 Feb 5; 11(1): 736. DOI: 10.1038/s41467-019-13885-w2041-1723http://hdl.handle.net/10230/44321The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements.application/pdfeng© 2020 Yiqun Zhang et al. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madeCàncerGenèticaGenòmicainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-019-13885-winfo:eu-repo/semantics/openAccess