Patterns of somatic structural variation in human cancer genomes
(2020) In Nature 578(7793). p.112-121- 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... (More)
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.
(Less)
- author
- contributor
- Borg, Åke LU ; Ringnér, Markus LU and Staaf, Johan LU
- author collaboration
- organization
- publishing date
- 2020-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Gene Rearrangement/genetics, Genetic Variation, Genome, Human/genetics, Genomics, Humans, Mutagenesis, Insertional, Neoplasms/genetics, Telomerase/genetics
- in
- Nature
- volume
- 578
- issue
- 7793
- pages
- 112 - 121
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85078674086
- pmid:32025012
- ISSN
- 0028-0836
- DOI
- 10.1038/s41586-019-1913-9
- language
- English
- LU publication?
- yes
- id
- 5ad43c7f-63e9-4e76-bae5-7ba7012fa3df
- date added to LUP
- 2023-03-29 17:15:08
- date last changed
- 2024-06-29 04:47:26
@article{5ad43c7f-63e9-4e76-bae5-7ba7012fa3df, abstract = {{<p>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.</p>}}, author = {{Li, Yilong and Roberts, Nicola D and Wala, Jeremiah A and Shapira, Ofer and Schumacher, Steven E and Kumar, Kiran and Khurana, Ekta and Waszak, Sebastian and Korbel, Jan O and Haber, James E and Imielinski, Marcin and Weischenfeldt, Joachim and Beroukhim, Rameen and Campbell, Peter J}}, issn = {{0028-0836}}, keywords = {{Gene Rearrangement/genetics; Genetic Variation; Genome, Human/genetics; Genomics; Humans; Mutagenesis, Insertional; Neoplasms/genetics; Telomerase/genetics}}, language = {{eng}}, number = {{7793}}, pages = {{112--121}}, publisher = {{Nature Publishing Group}}, series = {{Nature}}, title = {{Patterns of somatic structural variation in human cancer genomes}}, url = {{http://dx.doi.org/10.1038/s41586-019-1913-9}}, doi = {{10.1038/s41586-019-1913-9}}, volume = {{578}}, year = {{2020}}, }