Patterns of somatic structural variation in human cancer genomes
- PMID: 32025012
- PMCID: PMC7025897
- DOI: 10.1038/s41586-019-1913-9
Patterns of somatic structural variation in human cancer genomes
Erratum in
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Author Correction: Patterns of somatic structural variation in human cancer genomes.Nature. 2023 Feb;614(7948):E38. doi: 10.1038/s41586-022-05597-x. Nature. 2023. PMID: 36697835 Free PMC article. No abstract available.
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.
Conflict of interest statement
R.B. owns equity in Ampressa Therapeutics; M.M. is the scientific advisory board chair of—and consultant for— OrigiMed, and receives research funding from Bayer and Ono Pharma, and patent royalties from LabCorp.; J.W. is a consultant for Nference Inc.; C.-Z.Z. is a cofounder and equity holder of Pillar Biosciences, a for-profit company specializing in the development of targeted sequencing assays.
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Comment in
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Global genomics project unravels cancer's complexity at unprecedented scale.Nature. 2020 Feb;578(7793):39-40. doi: 10.1038/d41586-020-00213-2. Nature. 2020. PMID: 32025004 No abstract available.
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