| Title: |
Patterns of somatic structural variation in human cancer genomes |
| Authors: |
Li, Y; Roberts, ND; Wala, JA; Shapira, O; Schumacher, SE; Kumar, K; Khurana, E; Waszak, S; Korbel, JO; Haber, JE; Imielinski, M; Weischenfeldt, J; Beroukhim, R; Campbell, PJ; Akdemir, KC; Alvarez, EG; Baez-Ortega, A; Boutros, PC; Bowtell, DDL; Brors, B; Burns, KH; Chan, K; Chen, K; Cortés-Ciriano, I; Dueso-Barroso, A; Dunford, AJ; Edwards, PA; Estivill, X; Etemadmoghadam, D; Feuerbach, L; Fink, JL; Frenkel-Morgenstern, M; Garsed, DW; Gerstein, M; Gordenin, DA; Haan, D; Hess, JM; Hutter, B; Jones, DTW; Ju, YS; Kazanov, MD; Klimczak, LJ; Koh, Y; Lee, EA; Lee, JJK; Lynch, AG; Macintyre, G; Markowetz, F; Martincorena, I; Martinez-Fundichely, A; Meyerson, M; Miyano, S; Nakagawa, H; Navarro, FCP; Ossowski, S; Park, PJ; Pearson, JV; Puiggròs, M; Rippe, K; Roberts, SA; Rodriguez-Martin, B; Scully, R; Shackleton, M; Sidiropoulos, N; Sieverling, L; Stewart, C; Torrents, D; Tubio, JMC; Villasante, I; Waddell, N; Yang, L; Yao, X; Yoon, SS; Zamora, J; Zhang, CZ; Aaltonen, LA; Abascal, F; Abeshouse, A; Aburatani, H; Adams, DJ; Agrawal, N; Ahn, KS; Ahn, SM; Aikata, H; Akbani, R; Al-Ahmadie, H; Al-Sedairy, ST; Al-Shahrour, F; Alawi, M; Albert, M; Aldape, K; Alexandrov, LB; Ally, A; Alsop, K; Amary, F; Amin, SB; Aminou, B; Ammerpohl, O; Anderson, MJ; Ang, Y |
| Publisher Information: |
NATURE PORTFOLIO |
| Publication Year: |
2020 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0028-0836 |
| Relation: |
https://hdl.handle.net/11343/245677 |
| Availability: |
https://hdl.handle.net/11343/245677 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.79962E6D |
| Database: |
BASE |