Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
(2020) In Nature Genetics 52(3). p.306-319- Abstract
About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete... (More)
About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.
(Less)
- author
- contributor
- Borg, Åke
LU
; Ringnér, Markus
LU
and Staaf, Johan
LU
- author collaboration
- organization
- publishing date
- 2020-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Carcinogenesis/genetics, Gene Rearrangement/genetics, Genome, Human/genetics, Humans, Long Interspersed Nucleotide Elements/genetics, Neoplasms/genetics, Retroelements/genetics
- in
- Nature Genetics
- volume
- 52
- issue
- 3
- pages
- 306 - 319
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85079062163
- pmid:32024998
- ISSN
- 1546-1718
- DOI
- 10.1038/s41588-019-0562-0
- language
- English
- LU publication?
- yes
- id
- 2d5c311f-b39f-44a5-82d2-efba3c9160b6
- date added to LUP
- 2023-03-29 17:29:06
- date last changed
- 2024-04-18 19:41:25
@article{2d5c311f-b39f-44a5-82d2-efba3c9160b6,
abstract = {{<p>About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.</p>}},
author = {{Rodriguez-Martin, Bernardo and Alvarez, Eva G and Baez-Ortega, Adrian and Zamora, Jorge and Supek, Fran and Demeulemeester, Jonas and Santamarina, Martin and Ju, Young Seok and Temes, Javier and Garcia-Souto, Daniel and Detering, Harald and Li, Yilong and Rodriguez-Castro, Jorge and Dueso-Barroso, Ana and Bruzos, Alicia L and Dentro, Stefan C and Blanco, Miguel G and Contino, Gianmarco and Ardeljan, Daniel and Tojo, Marta and Roberts, Nicola D and Zumalave, Sonia and Edwards, Paul A and Weischenfeldt, Joachim and Puiggròs, Montserrat and Chong, Zechen and Chen, Ken and Lee, Eunjung Alice and Wala, Jeremiah A and Raine, Keiran M and Butler, Adam and Waszak, Sebastian M and Navarro, Fabio C P and Schumacher, Steven E and Monlong, Jean and Maura, Francesco and Bolli, Niccolo and Bourque, Guillaume and Gerstein, Mark and Park, Peter J and Wedge, David C and Beroukhim, Rameen and Torrents, David and Korbel, Jan O and Martincorena, Iñigo and Fitzgerald, Rebecca C and Van Loo, Peter and Kazazian, Haig H and Burns, Kathleen H and Campbell, Peter J and Tubio, Jose M C}},
issn = {{1546-1718}},
keywords = {{Carcinogenesis/genetics; Gene Rearrangement/genetics; Genome, Human/genetics; Humans; Long Interspersed Nucleotide Elements/genetics; Neoplasms/genetics; Retroelements/genetics}},
language = {{eng}},
number = {{3}},
pages = {{306--319}},
publisher = {{Nature Publishing Group}},
series = {{Nature Genetics}},
title = {{Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition}},
url = {{http://dx.doi.org/10.1038/s41588-019-0562-0}},
doi = {{10.1038/s41588-019-0562-0}},
volume = {{52}},
year = {{2020}},
}