Patterns of somatic structural variation in human cancer genomes
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- dc.contributor.author Li, Yilong
- dc.contributor.author Roberts, Nicola D.
- dc.contributor.author Wala, Jeremiah A.
- dc.contributor.author Shapira, Ofer
- dc.contributor.author Schumacher, Steven E.
- dc.contributor.author Kumar, Kiran
- dc.contributor.author Khurana, Ekta
- dc.contributor.author Waszak, Sebastian
- dc.contributor.author Korbel, Jan O.
- dc.contributor.author Haber, James E.
- dc.contributor.author Imielinski, Marcin
- dc.contributor.author PCAWG Structural Variation Working Group
- dc.contributor.author Weischenfeldt, Joachim
- dc.contributor.author Beroukhim, Rameen
- dc.contributor.author Campbell, Peter J.
- dc.contributor.author PCAWG Consortium
- dc.contributor.author Ossowski, Stephan
- dc.date.accessioned 2020-04-21T10:03:05Z
- dc.date.available 2020-04-21T10:03:05Z
- dc.date.issued 2020
- dc.description.abstract A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1-7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions-as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2-7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and-in liver cancer-frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.
- dc.description.sponsorship This work was supported by the Wellcome Trust, Pediatric Low-Grade Astrocytoma Fund and the Fund for Innovation in Cancer Informatics. P.J.C. is a Wellcome Trust Senior Clinical Fellow (WT088340MA)
- dc.format.mimetype application/pdf
- dc.identifier.citation Li Y, Roberts ND, Wala JA, Shapira O, Schumacher SE, Kumar K et al. Patterns of somatic structural variation in human cancer genomes. Nature. 2020 Feb; 578(7793): 112-121. DOI: 10.1038/s41586-019-1913-9
- dc.identifier.doi http://dx.doi.org/10.1038/s41586-019-1913-9
- dc.identifier.issn 0028-0836
- dc.identifier.uri http://hdl.handle.net/10230/44291
- dc.language.iso eng
- dc.publisher Nature Research
- dc.relation.ispartof Nature. 2020 Feb;578(7793):112-21
- dc.rights © 2020 Yilong Li 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 Genètica humana -- Variació
- dc.subject.other Genoma humà
- dc.subject.other Tumors
- dc.title Patterns of somatic structural variation in human cancer genomes
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion