TY - JOUR
T1 - Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
AU - PCAWG Structural Variation Working Group
AU - PCAWG Consortium
AU - Rodriguez-Martin, Bernardo
AU - Alvarez, Eva G.
AU - Baez-Ortega, Adrian
AU - Zamora, Jorge
AU - Supek, Fran
AU - Demeulemeester, Jonas
AU - Santamarina, Martin
AU - Ju, Young Seok
AU - Temes, Javier
AU - Garcia-Souto, Daniel
AU - Detering, Harald
AU - Li, Yilong
AU - Rodriguez-Castro, Jorge
AU - Dueso-Barroso, Ana
AU - Bruzos, Alicia L.
AU - Dentro, Stefan C.
AU - Blanco, Miguel G.
AU - Contino, Gianmarco
AU - Ardeljan, Daniel
AU - Tojo, Marta
AU - Roberts, Nicola D.
AU - Zumalave, Sonia
AU - Edwards, Paul A.
AU - Weischenfeldt, Joachim
AU - Puiggròs, Montserrat
AU - Chong, Zechen
AU - Chen, Ken
AU - Lee, Eunjung Alice
AU - Wala, Jeremiah A.
AU - Raine, Keiran M.
AU - Butler, Adam
AU - Waszak, Sebastian M.
AU - Navarro, Fabio C.P.
AU - Schumacher, Steven E.
AU - Monlong, Jean
AU - Maura, Francesco
AU - Bolli, Niccolo
AU - Bourque, Guillaume
AU - Gerstein, Mark
AU - Park, Peter J.
AU - Wedge, David C.
AU - Beroukhim, Rameen
AU - Torrents, David
AU - Korbel, Jan O.
AU - Martincorena, Iñigo
AU - Fitzgerald, Rebecca C.
AU - Van Loo, Peter
AU - Kazazian, Haig H.
AU - Burns, Kathleen H.
AU - Turner, Daniel J.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85079062163&partnerID=8YFLogxK
U2 - 10.1038/s41588-019-0562-0
DO - 10.1038/s41588-019-0562-0
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C2 - 32024998
AN - SCOPUS:85079062163
SN - 1061-4036
VL - 52
SP - 306
EP - 319
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -
