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dc.contributor.authorZhang, Yiqun
dc.contributor.authorChen, Fengju
dc.contributor.authorFonseca, Nuno A.
dc.contributor.authorHe, Yao
dc.contributor.authorFujita, Masashi
dc.contributor.authorNakagawa, Hidewaki
dc.contributor.authorZhang, Zemin
dc.contributor.authorPCAWG Transcriptome Working Group
dc.contributor.authorPCAWG Structural Variation Working Group
dc.contributor.authorCreighton, Chad J.
dc.contributor.authorPCAWG Consortium
dc.date.accessioned2020-03-19T13:30:01Z
dc.date.available2020-03-19T13:30:01Z
dc.date.issued2020-02-05
dc.identifier.citationZhang , Y , Chen , F , Fonseca , N A , He , Y , Fujita , M , Nakagawa , H , Zhang , Z , PCAWG Transcriptome Working Group , PCAWG Structural Variation Working Group , Creighton , C J & PCAWG Consortium 2020 , ' High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations ' , Nature Communications , vol. 11 , 736 . https://doi.org/10.1038/s41467-019-13885-wen
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 266944564
dc.identifier.otherPURE UUID: 89368297-1710-4e80-8665-63af2aeddda2
dc.identifier.otherScopus: 85079031729
dc.identifier.otherPubMed: 32024823
dc.identifier.otherORCID: /0000-0002-7876-7338/work/70920010
dc.identifier.urihttp://hdl.handle.net/10023/19680
dc.descriptionFunding: 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).en
dc.description.abstractThe 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.format.extent14
dc.language.isoeng
dc.relation.ispartofNature Communicationsen
dc.rightsCopyright © The Author(s) 2020. 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en
dc.subjectCancer genomicsen
dc.subjectGene expressionen
dc.subjectQH426 Geneticsen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectChemistry(all)en
dc.subjectBiochemistry, Genetics and Molecular Biology(all)en
dc.subjectPhysics and Astronomy(all)en
dc.subject3rd-DASen
dc.subject.lccQH426en
dc.subject.lccRC0254en
dc.titleHigh-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterationsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Statisticsen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.identifier.doihttps://doi.org/10.1038/s41467-019-13885-w
dc.description.statusPeer revieweden


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