High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations

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• dc.contributor.author Zhang, Yikun
• dc.contributor.author Chen, Fengju
• dc.contributor.author Fonseca, Nuno
• dc.contributor.author He, Yao
• dc.contributor.author Fujita, Masashi
• dc.contributor.author Nakagawa, Hidewaki
• dc.contributor.author Zhang, Zemin
• dc.contributor.author Brazma, Alvis
• dc.contributor.author PCAWG Transcriptome Working Group
• dc.contributor.author PCAWG Structural Variation Working Group
• dc.contributor.author Creighton, Chad J.
• dc.contributor.author PCAWG Consortium
• dc.contributor.author Ossowski, Stephan
• dc.date.accessioned 2020-04-24T07:19:03Z
• dc.date.available 2020-04-24T07:19:03Z
• dc.date.issued 2020
• dc.description.abstract The 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.
• dc.description.sponsorship This work was supported in part by National Institutes of Health (NIH) grant P30CA125123 (C. Creighton) and Cancer Prevention and Research Institute of Texas (CPRIT) grant RP120713 C2 (C. Creighton)
• dc.format.mimetype application/pdf
• dc.identifier.citation Zhang 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-w
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-13885-w
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/44321
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Communications. 2020 Feb 5;11(1):736
• dc.rights © 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 made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Càncer
• dc.subject.other Genètica
• dc.subject.other Genòmica
• dc.title High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion