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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.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 .
dc.identifier.otherORCID: /0000-0002-7876-7338/work/70920010
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.relation.ispartofNature Communicationsen
dc.subjectCancer genomicsen
dc.subjectGene expressionen
dc.subjectQH426 Geneticsen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectBiochemistry, Genetics and Molecular Biology(all)en
dc.subjectPhysics and Astronomy(all)en
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleHigh-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterationsen
dc.typeJournal articleen
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.description.statusPeer revieweden

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