Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
Creators: name: Alvarez, Eva G.
name: Baez-Ortega, Adrian
name: Zamora, Jorge
name: Supek, Fran
name: Demeulemeester, Jonas
name: Santamarina, Martin
name: Temes, Javier
name: Garcia-Souto, Daniel
name: Detering, Harald
name: Li, Yilong
name: Rodriguez-Castro, Jorge
name: Dueso-Barroso, Ana
name: Bruzos, Alicia L.
name: Dentro, Stefan C.
name: Blanco, Miguel G.
name: Contino, Gianmarco
name: Ardeljan, Daniel
name: Tojo, Marta
name: Zumalave, Sonia
name: Edwards, Paul A. W.
name: Puiggròs, Montserrat
name: Chong, Zechen
name: Lee, Eunjung Alice
name: Raine, Keiran
name: Butler, Adam
name: Waszak, Sebastian M.
name: Schumacher, Steven E.
name: Monlong, Jean
name: Maura, Francesco
name: Bolli, Niccolo
name: Bourque, Guillaume
name: Gerstein, Mark
name: Wedge, David C.
name: Beroukhim, Rameen
name: Torrents, David
name: Martincorena, Inigo
name: Fitzgerald, Rebecca C.
name: Van Loo, Peter
name: Kazazian, Haig H.
name: Tubio, Jose M. C.
name: Akdemir, Kadir C.
name: Boutros, Paul C.
name: Bowtell, David D. L.
name: Brors, Benedikt
name: Burns, Kathleen H.
name: Campbell, Peter J.
name: Chan, Kin
name: Chen, Ken
name: Cortés-Ciriano, Isidro
name: Dunford, Andrew J.
name: Edwards, Paul A.
name: Estivill, Xavier
name: Etemadmoghadam, Dariush
name: Feuerbach, Lars
name: Fink, J. Lynn
name: Frenkel-Morgenstern, Milana
name: Garsed, Dale W.
name: Gordenin, Dmitry A.
name: Haan, David
name: Haber, James E.
name: Hess, Julian M.
name: Hutter, Barbara
name: Imielinski, Marcin
name: Jones, David T. W.
name: Ju, Young Seok
name: Kazanov, Marat D.
name: Klimczak, Leszek J.
name: Koh, Youngil
name: Korbel, Jan O.
name: Kumar, Kiran
name: Lee, Jake June-Koo
name: Lynch, Andy G.
name: Macintyre, Geoff
name: Markowetz, Florian
name: Martincorena, Iñigo
name: Martinez-Fundichely, Alexander
name: Meyerson, Matthew
name: Miyano, Satoru
name: Nakagawa, Hidewaki
name: Navarro, Fabio C. P.
name: Ossowski, Stephan
name: Park, Peter J.
name: Pearson, John V.
name: Rippe, Karsten
name: Roberts, Nicola D.
name: Roberts, Steven A.
name: Rodriguez-Martin, Bernardo
name: Scully, Ralph
name: Shackleton, Mark
name: Sidiropoulos, Nikos
name: Sieverling, Lina
name: Stewart, Chip
name: Tubio, Jose M. C.
name: Villasante, Izar
name: Waddell, Nicola
name: Wala, Jeremiah A.
name: Weischenfeldt, Joachim
name: Yang, Lixing
name: Yao, Xiaotong
name: Yoon, Sung-Soo
name: Zhang, Cheng-Zhong
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Article
/692/699/67
/631/208/212
/45/23
/45
article

description: Funder: Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Ministry of Culture, Education and University Planning, Government of Galicia); doi: https://doi.org/10.13039/501100008425
description: Funder: Ministerio de Educación, Cultura y Deporte (Ministry of Education, Culture and Sports, Spain); doi: https://doi.org/10.13039/501100003176
description: Funder: EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council); doi: https://doi.org/10.13039/100010663
description: Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329
description: Funder: Korea Health Industry Development Institute (KHIDI); doi: https://doi.org/10.13039/501100003710
description: Funder: Danish Medical Research Council
description: Funder: NIH
description: Funder: Associazione Italiana Contro le Leucemie-Linfomi e Mieloma
description: Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289
description: 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 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.