PT  - JOURNAL ARTICLE
AU  - Bernardo Rodriguez-Martin
AU  - Eva G. Alvarez
AU  - Adrian Baez-Ortega
AU  - Jonas Demeulemeester
AU  - Young Seok Ju
AU  - Jorge Zamora
AU  - Harald Detering
AU  - Yilong Li
AU  - Gianmarco Contino
AU  - Stefan C. Dentro
AU  - Alicia L. Bruzos
AU  - Ana Dueso-Barroso
AU  - Daniel Ardeljan
AU  - Marta Tojo
AU  - Nicola D. Roberts
AU  - Miguel G. Blanco
AU  - Paul A. W. Edwards
AU  - Joachim Weischenfeldt
AU  - Martin Santamarina
AU  - Montserrat Puiggros
AU  - Zechen Chong
AU  - Ken Chen
AU  - Eunjung Alice Lee
AU  - Jeremiah A. Wala
AU  - Keiran Raine
AU  - Adam Butler
AU  - Sebastian M. Waszak
AU  - Fabio C. P. Navarro
AU  - Steven E. Schumacher
AU  - Jean Monlong
AU  - Francesco Maura
AU  - Niccolo Bolli
AU  - Guillaume Bourque
AU  - Mark Gerstein
AU  - Peter J. Park
AU  - Rameen Berroukhim
AU  - David Torrents
AU  - Jan O. Korbel
AU  - Inigo Martincorena
AU  - Rebecca C. Fitzgerald
AU  - Peter Van Loo
AU  - Haig H. Kazazian
AU  - Kathleen H. Burns
AU  - Peter J. Campbell
AU  - Jose M. C. Tubio
AU  - on behalf of the PCAWG Structural Variation Working Group
AU  - ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
TI  - Pan-cancer analysis of whole genomes reveals driver rearrangements promoted by LINE-1 retrotransposition in human tumours
AID  - 10.1101/179705
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 179705
4099  - http://biorxiv.org/content/early/2017/08/24/179705.short
4100  - http://biorxiv.org/content/early/2017/08/24/179705.full
AB  - About half of all cancers have somatic integrations of retrotransposons. To characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,774 cancer genomes from 37 histological cancer subtypes. We identified 20,230 somatically acquired retrotransposition events, affecting 43% of samples, and spanning a range of event types. L1 insertions emerged as the third most frequent type of somatic structural variation in cancer. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, sometimes removing tumour suppressor genes, as well as inducing complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles of genomic instability, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications in the initiation and/or development of human tumours.