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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, Yiqun | |
dc.contributor.author | Chen, Fengju | |
dc.contributor.author | Fonseca, Nuno A. | |
dc.contributor.author | He, Yao | |
dc.contributor.author | Fujita, Masashi | |
dc.contributor.author | Nakagawa, Hidewaki | |
dc.contributor.author | Zhang, Zemin | |
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.date.accessioned | 2020-03-19T13:30:01Z | |
dc.date.available | 2020-03-19T13:30:01Z | |
dc.date.issued | 2020-02-05 | |
dc.identifier | 266944564 | |
dc.identifier | 89368297-1710-4e80-8665-63af2aeddda2 | |
dc.identifier | 85079031729 | |
dc.identifier | 32024823 | |
dc.identifier.citation | Zhang , 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-w | en |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | ORCID: /0000-0002-7876-7338/work/70920010 | |
dc.identifier.uri | https://hdl.handle.net/10023/19680 | |
dc.description | Funding: 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.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.format.extent | 14 | |
dc.format.extent | 1507968 | |
dc.language.iso | eng | |
dc.relation.ispartof | Nature Communications | en |
dc.subject | Cancer genomics | en |
dc.subject | Gene expression | en |
dc.subject | QH426 Genetics | en |
dc.subject | RC0254 Neoplasms. Tumors. Oncology (including Cancer) | en |
dc.subject | Chemistry(all) | en |
dc.subject | Biochemistry, Genetics and Molecular Biology(all) | en |
dc.subject | Physics and Astronomy(all) | en |
dc.subject | 3rd-DAS | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | QH426 | en |
dc.subject.lcc | RC0254 | en |
dc.title | High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Statistics | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Cellular Medicine Division | en |
dc.identifier.doi | 10.1038/s41467-019-13885-w | |
dc.description.status | Peer reviewed | en |
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