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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.authorBrazma, Alvis
dc.contributor.authorPCAWG Transcriptome Working Group
dc.contributor.authorPCAWG Structural Variation Working Group
dc.contributor.authorCreighton, Chad J
dc.contributor.authorPCAWG Consortium
dc.date.accessioned2021-02-04T16:23:58Z
dc.date.available2021-02-04T16:23:58Z
dc.date.issued2020-02-05
dc.date.submitted2017-12-22
dc.identifier.issn2041-1723
dc.identifier.others41467-019-13885-w
dc.identifier.other13885
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/317142
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.languageen
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectArticle
dc.subject/631/67/69
dc.subject/631/208/199
dc.subject/45/23
dc.subject/45/91
dc.subjectarticle
dc.titleHigh-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.
dc.typeArticle
dc.date.updated2021-02-04T16:23:57Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume11
dc.identifier.doi10.17863/CAM.64253
dcterms.dateAccepted2019-12-04
rioxxterms.versionofrecord10.1038/s41467-019-13885-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidFonseca, Nuno A [0000-0003-4832-578X]
dc.contributor.orcidFujita, Masashi [0000-0002-1457-6233]
dc.contributor.orcidBrazma, Alvis [0000-0001-5988-7409]
dc.contributor.orcidCreighton, Chad J [0000-0002-6090-703X]
dc.identifier.eissn2041-1723
pubs.funder-project-idU.S. Department of Health & Human Services | National Institutes of Health (NIH) (CA125123)
pubs.funder-project-idCancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) (RP120713)
cam.issuedOnline2020-02-05


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)