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Patterns of somatic structural variation in human cancer genomes

Li, Yilong; Roberts, Nicola D; Wala, Jeremiah A; Shapira, Ofer; Schumacher, Steven E; Kumar, Kiran; Khurana, Ekta; ... Campbell, Peter J; + view all (2020) Patterns of somatic structural variation in human cancer genomes. Nature , 578 (7793) pp. 112-121. 10.1038/s41586-019-1913-9. Green open access

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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 chromosomes1,2,3,4,5,6,7. 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.

Type: Article
Title: Patterns of somatic structural variation in human cancer genomes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41586-019-1913-9
Publisher version: https://doi.org/10.1038/s41586-019-1913-9
Language: English
Additional information: © 2022 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Cancer genomics, Genomic instability
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10148067
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