Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.

Bernardo Rodriguez-Martin, Eva G. Alvarez, Adrian Baez-Ortega, Jorge Zamora, Fran Supek, Jonas Demeulemeester, Martin Santamarina, Young Seok Ju, Javier Temes, Daniel Garcia-Souto, Harald Detering, Yilong Li, Jorge Rodriguez-Castro, Ana Dueso-Barroso, Alicia L. Bruzos, Stefan C. Dentro, Miguel G. Blanco, Gianmarco Contino, Daniel Ardeljan, Marta TojoNicola D. Roberts, Sonia Zumalave, Paul A. W. Edwards, Joachim Weischenfeldt, Montserrat Puiggròs, Zechen Chong, Ken Chen, Eunjung Alice Lee, Jeremiah A. Wala, Keiran Raine, Adam Butler, Sebastian M. Waszak, Fabio C. P. Navarro, Steven E. Schumacher, Jean Monlong, Francesco Maura, Niccolo Bolli, Guillaume Bourque, Mark Gerstein, Peter J. Park, David C. Wedge, Rameen Beroukhim, David Torrents, Jan O. Korbel, Inigo Martincorena, Rebecca C. Fitzgerald, Peter Van Loo, Haig H. Kazazian, Kathleen H. Burns, Peter J. Campbell, Jose M. C. Tubio

Research output: Contribution to journalArticlepeer-review


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 35LINE-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.
Original languageEnglish
JournalNature Genetics
Issue number3
Publication statusPublished - Mar 1 2020


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