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

PCAWG-Structural Variation Working Group; PCAWG Consortium; 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 Tojo; Nicola D. Roberts; Sonia Zumalave; Paul A. Edwards; Joachim Weischenfeldt; Montserrat Puiggròs; Zechen Chong; Ken Chen; Eunjung Alice Lee; Jeremiah A. Wala; Keiran M. 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; Iñigo Martincorena; Rebecca C. Fitzgerald; Peter Van Loo; Haig H. Kazazian; Kathleen H. Burns; Peter J. Campbell; Jose M.C. Tubio; Kadir C. Akdemir; Paul C. Boutros; David D.L. Bowtell; Benedikt Brors; Kin Chan; Isidro Cortés-Ciriano; Andrew J. Dunford; Xavier Estivill; Dariush Etemadmoghadam; Lars Feuerbach; J. Lynn Fink; Milana Frenkel-Morgenstern; Dale W. Garsed; Dmitry A. Gordenin; David Haan; James E. Haber; Julian M. Hess; Barbara Hutter; Marcin Imielinski; David T.W. Jones; Marat D. Kazanov; Leszek J. Klimczak; Youngil Koh; Kiran Kumar; Jake June Koo Lee; Andy G. Lynch; Geoff Macintyre; Florian Markowetz; Alexander Martinez-Fundichely; Matthew Meyerson; Satoru Miyano; Hidewaki Nakagawa; Stephan Ossowski; John V. Pearson; Karsten Rippe; Steven A. Roberts; Ralph Scully; Mark Shackleton; Nikos Sidiropoulos; Lina Sieverling; Chip Stewart; Izar Villasante; Nicola Waddell; Lixing Yang; Xiaotong Yao; Sung Soo Yoon; Cheng Zhong Zhang; Lauri A. Aaltonen; Federico Abascal; Adam Abeshouse; Hiroyuki Aburatani; David J. Adams; Nishant Agrawal; Keun Soo Ahn; Sung Min Ahn; Hiroshi Aikata; Rehan Akbani; Hikmat Al-Ahmadie; Sultan T. Al-Sedairy; Fatima Al-Shahrour; Malik Alawi; Monique Albert; Kenneth Aldape; Ludmil B. Alexandrov; Adrian Ally; Kathryn Alsop; Fernanda Amary; Samirkumar B. Amin; Brice Aminou; Ole Ammerpohl; Matthew J. Anderson; Yeng Ang; Davide Antonello; Pavana Anur; Samuel Aparicio; Elizabeth L. Appelbaum; Yasuhito Arai; Axel Aretz; Koji Arihiro; Shun Ichi Ariizumi; Joshua Armenia; Laurent Arnould; Sylvia Asa; Yassen Assenov; Gurnit Atwal; Sietse Aukema; J. Todd Auman; Miriam R.R. Aure; Philip Awadalla; Marta Aymerich; Gary D. Bader; Matthew H. Bailey; Peter J. Bailey; Miruna Balasundaram; Saianand Balu; Pratiti Bandopadhayay; Rosamonde E. Banks; Stefano Barbi; Andrew P. Barbour; Jonathan Barenboim; Jill Barnholtz-Sloan; Hugh Barr; Elisabet Barrera; John Bartlett; Javier Bartolome; Claudio Bassi; Oliver F. Bathe; Daniel Baumhoer; Prashant Bavi; Stephen B. Baylin; Wojciech Bazant; Duncan Beardsmore; Timothy A. Beck; Sam Behjati; Andreas Behren; Beifang Niu; Cindy Bell; Sergi Beltran; Christopher Benz; Andrew Berchuck; Anke K. Bergmann; Erik N. Bergstrom; Benjamin P. Berman; Daniel M. Berney; Stephan H. Bernhart; Mario Berrios; Samantha Bersani; Johanna Bertl; Miguel Betancourt; Vinayak Bhandari; Shriram G. Bhosle; Andrew V. Biankin; Matthias Bieg; Darell Bigner; Hans Binder; Ewan Birney; Michael Birrer; Nidhan K. Biswas; Bodil Bjerkehagen; Tom Bodenheimer; Li Ding; Lucinda A. Fulton; Robert S. Fulton; Ramaswamy Govindan; Reyka Jayasinghe; Tim Ley; Christopher A. Miller; David Mutch; Michael C. Wendl

doi:10.1038/s41588-019-0562-0

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

PCAWG-Structural Variation Working Group, PCAWG Consortium, 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 ContinoDaniel Ardeljan, Marta Tojo, Nicola D. Roberts, Sonia Zumalave, Paul A. Edwards, Joachim Weischenfeldt, Montserrat Puiggròs, Zechen Chong, Ken Chen, Eunjung Alice Lee, Jeremiah A. Wala, Keiran M. 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, Iñigo Martincorena, Rebecca C. Fitzgerald, Peter Van Loo, Haig H. Kazazian, Kathleen H. Burns, Peter J. Campbell, Jose M.C. Tubio, Kadir C. Akdemir, Paul C. Boutros, David D.L. Bowtell, Benedikt Brors, Kin Chan, Isidro Cortés-Ciriano, Andrew J. Dunford, Xavier Estivill, Dariush Etemadmoghadam, Lars Feuerbach, J. Lynn Fink, Milana Frenkel-Morgenstern, Dale W. Garsed, Dmitry A. Gordenin, David Haan, James E. Haber, Julian M. Hess, Barbara Hutter, Marcin Imielinski, David T.W. Jones, Marat D. Kazanov, Leszek J. Klimczak, Youngil Koh, Kiran Kumar, Jake June Koo Lee, Andy G. Lynch, Geoff Macintyre, Florian Markowetz, Alexander Martinez-Fundichely, Matthew Meyerson, Satoru Miyano, Hidewaki Nakagawa, Stephan Ossowski, John V. Pearson, Karsten Rippe, Steven A. Roberts, Ralph Scully, Mark Shackleton, Nikos Sidiropoulos, Lina Sieverling, Chip Stewart, Izar Villasante, Nicola Waddell, Lixing Yang, Xiaotong Yao, Sung Soo Yoon, Cheng Zhong Zhang, Lauri A. Aaltonen, Federico Abascal, Adam Abeshouse, Hiroyuki Aburatani, David J. Adams, Nishant Agrawal, Keun Soo Ahn, Sung Min Ahn, Hiroshi Aikata, Rehan Akbani, Hikmat Al-Ahmadie, Sultan T. Al-Sedairy, Fatima Al-Shahrour, Malik Alawi, Monique Albert, Kenneth Aldape, Ludmil B. Alexandrov, Adrian Ally, Kathryn Alsop, Fernanda Amary, Samirkumar B. Amin, Brice Aminou, Ole Ammerpohl, Matthew J. Anderson, Yeng Ang, Davide Antonello, Pavana Anur, Samuel Aparicio, Elizabeth L. Appelbaum, Yasuhito Arai, Axel Aretz, Koji Arihiro, Shun Ichi Ariizumi, Joshua Armenia, Laurent Arnould, Sylvia Asa, Yassen Assenov, Gurnit Atwal, Sietse Aukema, J. Todd Auman, Miriam R.R. Aure, Philip Awadalla, Marta Aymerich, Gary D. Bader, Matthew H. Bailey, Peter J. Bailey, Miruna Balasundaram, Saianand Balu, Pratiti Bandopadhayay, Rosamonde E. Banks, Stefano Barbi, Andrew P. Barbour, Jonathan Barenboim, Jill Barnholtz-Sloan, Hugh Barr, Elisabet Barrera, John Bartlett, Javier Bartolome, Claudio Bassi, Oliver F. Bathe, Daniel Baumhoer, Prashant Bavi, Stephen B. Baylin, Wojciech Bazant, Duncan Beardsmore, Timothy A. Beck, Sam Behjati, Andreas Behren, Beifang Niu, Cindy Bell, Sergi Beltran, Christopher Benz, Andrew Berchuck, Anke K. Bergmann, Erik N. Bergstrom, Benjamin P. Berman, Daniel M. Berney, Stephan H. Bernhart, Mario Berrios, Samantha Bersani, Johanna Bertl, Miguel Betancourt, Vinayak Bhandari, Shriram G. Bhosle, Andrew V. Biankin, Matthias Bieg, Darell Bigner, Hans Binder, Ewan Birney, Michael Birrer, Nidhan K. Biswas, Bodil Bjerkehagen, Tom Bodenheimer, Li Ding, Lucinda A. Fulton, Robert S. Fulton, Ramaswamy Govindan, Reyka Jayasinghe, Tim Ley, Christopher A. Miller, David Mutch, Michael C. Wendl

Research output: Contribution to journal › Article › peer-review

258 Scopus citations

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.

Original language	English
Pages (from-to)	306-319
Number of pages	14
Journal	Nature Genetics
Volume	52
Issue number	3
DOIs	https://doi.org/10.1038/s41588-019-0562-0
State	Published - Mar 1 2020

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10.1038/s41588-019-0562-0

Cite this

PCAWG-Structural Variation Working Group, PCAWG Consortium, Rodriguez-Martin, B., Alvarez, E. G., Baez-Ortega, A., Zamora, J., Supek, F., Demeulemeester, J., Santamarina, M., Ju, Y. S., Temes, J., Garcia-Souto, D., Detering, H., Li, Y., Rodriguez-Castro, J., Dueso-Barroso, A., Bruzos, A. L., Dentro, S. C., Blanco, M. G., ... Wendl, M. C. (2020). Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. Nature Genetics, 52(3), 306-319. https://doi.org/10.1038/s41588-019-0562-0

@article{eb8f9018c67644c18e7b60c99f53dc4b,

title = "Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition",

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.",

author = "{PCAWG-Structural Variation Working Group} and {PCAWG Consortium} and Bernardo Rodriguez-Martin and Alvarez, {Eva G.} and Adrian Baez-Ortega and Jorge Zamora and Fran Supek and Jonas Demeulemeester and Martin Santamarina and Ju, {Young Seok} and Javier Temes and Daniel Garcia-Souto and Harald Detering and Yilong Li and Jorge Rodriguez-Castro and Ana Dueso-Barroso and Bruzos, {Alicia L.} and Dentro, {Stefan C.} and Blanco, {Miguel G.} and Gianmarco Contino and Daniel Ardeljan and Marta Tojo and Roberts, {Nicola D.} and Sonia Zumalave and Edwards, {Paul A.} and Joachim Weischenfeldt and Montserrat Puiggr{\`o}s and Zechen Chong and Ken Chen and Lee, {Eunjung Alice} and Wala, {Jeremiah A.} and Raine, {Keiran M.} and Adam Butler and Waszak, {Sebastian M.} and Navarro, {Fabio C.P.} and Schumacher, {Steven E.} and Jean Monlong and Francesco Maura and Niccolo Bolli and Guillaume Bourque and Mark Gerstein and Park, {Peter J.} and Wedge, {David C.} and Rameen Beroukhim and David Torrents and Korbel, {Jan O.} and I{\~n}igo Martincorena 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.} and Akdemir, {Kadir C.} and Boutros, {Paul C.} and Bowtell, {David D.L.} and Benedikt Brors and Kin Chan and Isidro Cort{\'e}s-Ciriano and Dunford, {Andrew J.} and Xavier Estivill and Dariush Etemadmoghadam and Lars Feuerbach and Fink, {J. Lynn} and Milana Frenkel-Morgenstern and Garsed, {Dale W.} and Gordenin, {Dmitry A.} and David Haan and Haber, {James E.} and Hess, {Julian M.} and Barbara Hutter and Marcin Imielinski and Jones, {David T.W.} and Kazanov, {Marat D.} and Klimczak, {Leszek J.} and Youngil Koh and Kiran Kumar and Lee, {Jake June Koo} and Lynch, {Andy G.} and Geoff Macintyre and Florian Markowetz and Alexander Martinez-Fundichely and Matthew Meyerson and Satoru Miyano and Hidewaki Nakagawa and Stephan Ossowski and Pearson, {John V.} and Karsten Rippe and Roberts, {Steven A.} and Ralph Scully and Mark Shackleton and Nikos Sidiropoulos and Lina Sieverling and Chip Stewart and Izar Villasante and Nicola Waddell and Lixing Yang and Xiaotong Yao and Yoon, {Sung Soo} and Zhang, {Cheng Zhong} and Aaltonen, {Lauri A.} and Federico Abascal and Adam Abeshouse and Hiroyuki Aburatani and Adams, {David J.} and Nishant Agrawal and Ahn, {Keun Soo} and Ahn, {Sung Min} and Hiroshi Aikata and Rehan Akbani and Hikmat Al-Ahmadie and Al-Sedairy, {Sultan T.} and Fatima Al-Shahrour and Malik Alawi and Monique Albert and Kenneth Aldape and Alexandrov, {Ludmil B.} and Adrian Ally and Kathryn Alsop and Fernanda Amary and Amin, {Samirkumar B.} and Brice Aminou and Ole Ammerpohl and Anderson, {Matthew J.} and Yeng Ang and Davide Antonello and Pavana Anur and Samuel Aparicio and Appelbaum, {Elizabeth L.} and Yasuhito Arai and Axel Aretz and Koji Arihiro and Ariizumi, {Shun Ichi} and Joshua Armenia and Laurent Arnould and Sylvia Asa and Yassen Assenov and Gurnit Atwal and Sietse Aukema and Auman, {J. Todd} and Aure, {Miriam R.R.} and Philip Awadalla and Marta Aymerich and Bader, {Gary D.} and Bailey, {Matthew H.} and Bailey, {Peter J.} and Miruna Balasundaram and Saianand Balu and Pratiti Bandopadhayay and Banks, {Rosamonde E.} and Stefano Barbi and Barbour, {Andrew P.} and Jonathan Barenboim and Jill Barnholtz-Sloan and Hugh Barr and Elisabet Barrera and John Bartlett and Javier Bartolome and Claudio Bassi and Bathe, {Oliver F.} and Daniel Baumhoer and Prashant Bavi and Baylin, {Stephen B.} and Wojciech Bazant and Duncan Beardsmore and Beck, {Timothy A.} and Sam Behjati and Andreas Behren and Beifang Niu and Cindy Bell and Sergi Beltran and Christopher Benz and Andrew Berchuck and Bergmann, {Anke K.} and Bergstrom, {Erik N.} and Berman, {Benjamin P.} and Berney, {Daniel M.} and Bernhart, {Stephan H.} and Mario Berrios and Samantha Bersani and Johanna Bertl and Miguel Betancourt and Vinayak Bhandari and Bhosle, {Shriram G.} and Biankin, {Andrew V.} and Matthias Bieg and Darell Bigner and Hans Binder and Ewan Birney and Michael Birrer and Biswas, {Nidhan K.} and Bodil Bjerkehagen and Tom Bodenheimer and Li Ding and Fulton, {Lucinda A.} and Fulton, {Robert S.} and Ramaswamy Govindan and Reyka Jayasinghe and Tim Ley and Miller, {Christopher A.} and David Mutch and Wendl, {Michael C.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = mar,

day = "1",

doi = "10.1038/s41588-019-0562-0",

language = "English",

volume = "52",

pages = "306--319",

journal = "Nature Genetics",

issn = "1061-4036",

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PCAWG-Structural Variation Working Group, PCAWG Consortium, Rodriguez-Martin, B, Alvarez, EG, Baez-Ortega, A, Zamora, J, Supek, F, Demeulemeester, J, Santamarina, M, Ju, YS, Temes, J, Garcia-Souto, D, Detering, H, Li, Y, Rodriguez-Castro, J, Dueso-Barroso, A, Bruzos, AL, Dentro, SC, Blanco, MG, Contino, G, Ardeljan, D, Tojo, M, Roberts, ND, Zumalave, S, Edwards, PA, Weischenfeldt, J, Puiggròs, M, Chong, Z, Chen, K, Lee, EA, Wala, JA, Raine, KM, Butler, A, Waszak, SM, Navarro, FCP, Schumacher, SE, Monlong, J, Maura, F, Bolli, N, Bourque, G, Gerstein, M, Park, PJ, Wedge, DC, Beroukhim, R, Torrents, D, Korbel, JO, Martincorena, I, Fitzgerald, RC, Van Loo, P, Kazazian, HH, Burns, KH, Campbell, PJ, Tubio, JMC, Akdemir, KC, Boutros, PC, Bowtell, DDL, Brors, B, Chan, K, Cortés-Ciriano, I, Dunford, AJ, Estivill, X, Etemadmoghadam, D, Feuerbach, L, Fink, JL, Frenkel-Morgenstern, M, Garsed, DW, Gordenin, DA, Haan, D, Haber, JE, Hess, JM, Hutter, B, Imielinski, M, Jones, DTW, Kazanov, MD, Klimczak, LJ, Koh, Y, Kumar, K, Lee, JJK, Lynch, AG, Macintyre, G, Markowetz, F, Martinez-Fundichely, A, Meyerson, M, Miyano, S, Nakagawa, H, Ossowski, S, Pearson, JV, Rippe, K, Roberts, SA, Scully, R, Shackleton, M, Sidiropoulos, N, Sieverling, L, Stewart, C, Villasante, I, Waddell, N, Yang, L, Yao, X, Yoon, SS, Zhang, CZ, Aaltonen, LA, Abascal, F, Abeshouse, A, Aburatani, H, Adams, DJ, Agrawal, N, Ahn, KS, Ahn, SM, Aikata, H, Akbani, R, Al-Ahmadie, H, Al-Sedairy, ST, Al-Shahrour, F, Alawi, M, Albert, M, Aldape, K, Alexandrov, LB, Ally, A, Alsop, K, Amary, F, Amin, SB, Aminou, B, Ammerpohl, O, Anderson, MJ, Ang, Y, Antonello, D, Anur, P, Aparicio, S, Appelbaum, EL, Arai, Y, Aretz, A, Arihiro, K, Ariizumi, SI, Armenia, J, Arnould, L, Asa, S, Assenov, Y, Atwal, G, Aukema, S, Auman, JT, Aure, MRR, Awadalla, P, Aymerich, M, Bader, GD, Bailey, MH, Bailey, PJ, Balasundaram, M, Balu, S, Bandopadhayay, P, Banks, RE, Barbi, S, Barbour, AP, Barenboim, J, Barnholtz-Sloan, J, Barr, H, Barrera, E, Bartlett, J, Bartolome, J, Bassi, C, Bathe, OF, Baumhoer, D, Bavi, P, Baylin, SB, Bazant, W, Beardsmore, D, Beck, TA, Behjati, S, Behren, A, Niu, B, Bell, C, Beltran, S, Benz, C, Berchuck, A, Bergmann, AK, Bergstrom, EN, Berman, BP, Berney, DM, Bernhart, SH, Berrios, M, Bersani, S, Bertl, J, Betancourt, M, Bhandari, V, Bhosle, SG, Biankin, AV, Bieg, M, Bigner, D, Binder, H, Birney, E, Birrer, M, Biswas, NK, Bjerkehagen, B, Bodenheimer, T, Ding, L , Fulton, LA , Fulton, RS , Govindan, R , Jayasinghe, R , Ley, T , Miller, CA , Mutch, D & Wendl, MC 2020, 'Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition', Nature Genetics, vol. 52, no. 3, pp. 306-319. https://doi.org/10.1038/s41588-019-0562-0

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 - Campbell, Peter J.

AU - Tubio, Jose M.C.

AU - Akdemir, Kadir C.

AU - Boutros, Paul C.

AU - Bowtell, David D.L.

AU - Brors, Benedikt

AU - Chan, Kin

AU - Cortés-Ciriano, Isidro

AU - Dunford, Andrew J.

AU - Estivill, Xavier

AU - Etemadmoghadam, Dariush

AU - Feuerbach, Lars

AU - Fink, J. Lynn

AU - Frenkel-Morgenstern, Milana

AU - Garsed, Dale W.

AU - Gordenin, Dmitry A.

AU - Haan, David

AU - Haber, James E.

AU - Hess, Julian M.

AU - Hutter, Barbara

AU - Imielinski, Marcin

AU - Jones, David T.W.

AU - Kazanov, Marat D.

AU - Klimczak, Leszek J.

AU - Koh, Youngil

AU - Kumar, Kiran

AU - Lee, Jake June Koo

AU - Lynch, Andy G.

AU - Macintyre, Geoff

AU - Markowetz, Florian

AU - Martinez-Fundichely, Alexander

AU - Meyerson, Matthew

AU - Miyano, Satoru

AU - Nakagawa, Hidewaki

AU - Ossowski, Stephan

AU - Pearson, John V.

AU - Rippe, Karsten

AU - Roberts, Steven A.

AU - Scully, Ralph

AU - Shackleton, Mark

AU - Sidiropoulos, Nikos

AU - Sieverling, Lina

AU - Stewart, Chip

AU - Villasante, Izar

AU - Waddell, Nicola

AU - Yang, Lixing

AU - Yao, Xiaotong

AU - Yoon, Sung Soo

AU - Zhang, Cheng Zhong

AU - Aaltonen, Lauri A.

AU - Abascal, Federico

AU - Abeshouse, Adam

AU - Aburatani, Hiroyuki

AU - Adams, David J.

AU - Agrawal, Nishant

AU - Ahn, Keun Soo

AU - Ahn, Sung Min

AU - Aikata, Hiroshi

AU - Akbani, Rehan

AU - Al-Ahmadie, Hikmat

AU - Al-Sedairy, Sultan T.

AU - Al-Shahrour, Fatima

AU - Alawi, Malik

AU - Albert, Monique

AU - Aldape, Kenneth

AU - Alexandrov, Ludmil B.

AU - Ally, Adrian

AU - Alsop, Kathryn

AU - Amary, Fernanda

AU - Amin, Samirkumar B.

AU - Aminou, Brice

AU - Ammerpohl, Ole

AU - Anderson, Matthew J.

AU - Ang, Yeng

AU - Antonello, Davide

AU - Anur, Pavana

AU - Aparicio, Samuel

AU - Appelbaum, Elizabeth L.

AU - Arai, Yasuhito

AU - Aretz, Axel

AU - Arihiro, Koji

AU - Ariizumi, Shun Ichi

AU - Armenia, Joshua

AU - Arnould, Laurent

AU - Asa, Sylvia

AU - Assenov, Yassen

AU - Atwal, Gurnit

AU - Aukema, Sietse

AU - Auman, J. Todd

AU - Aure, Miriam R.R.

AU - Awadalla, Philip

AU - Aymerich, Marta

AU - Bader, Gary D.

AU - Bailey, Matthew H.

AU - Bailey, Peter J.

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Bandopadhayay, Pratiti

AU - Banks, Rosamonde E.

AU - Barbi, Stefano

AU - Barbour, Andrew P.

AU - Barenboim, Jonathan

AU - Barnholtz-Sloan, Jill

AU - Barr, Hugh

AU - Barrera, Elisabet

AU - Bartlett, John

AU - Bartolome, Javier

AU - Bassi, Claudio

AU - Bathe, Oliver F.

AU - Baumhoer, Daniel

AU - Bavi, Prashant

AU - Baylin, Stephen B.

AU - Bazant, Wojciech

AU - Beardsmore, Duncan

AU - Beck, Timothy A.

AU - Behjati, Sam

AU - Behren, Andreas

AU - Niu, Beifang

AU - Bell, Cindy

AU - Beltran, Sergi

AU - Benz, Christopher

AU - Berchuck, Andrew

AU - Bergmann, Anke K.

AU - Bergstrom, Erik N.

AU - Berman, Benjamin P.

AU - Berney, Daniel M.

AU - Bernhart, Stephan H.

AU - Berrios, Mario

AU - Bersani, Samantha

AU - Bertl, Johanna

AU - Betancourt, Miguel

AU - Bhandari, Vinayak

AU - Bhosle, Shriram G.

AU - Biankin, Andrew V.

AU - Bieg, Matthias

AU - Bigner, Darell

AU - Binder, Hans

AU - Birney, Ewan

AU - Birrer, Michael

AU - Biswas, Nidhan K.

AU - Bjerkehagen, Bodil

AU - Bodenheimer, Tom

AU - Ding, Li

AU - Fulton, Lucinda A.

AU - Fulton, Robert S.

AU - Govindan, Ramaswamy

AU - Jayasinghe, Reyka

AU - Ley, Tim

AU - Miller, Christopher A.

AU - Mutch, David

AU - Wendl, Michael C.

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

M3 - Article

C2 - 32024998

AN - SCOPUS:85079062163

SN - 1061-4036

VL - 52

SP - 306

EP - 319

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

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

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