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 Tojo; Nicola 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

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

Fondazione IRCCS Istituto Nazionale dei Tumori

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

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 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 language	English
Journal	Nature Genetics
Issue number	3
Publication status	Published - Mar 1 2020

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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., Contino, G., Ardeljan, D., ... Tubio, J. M. C. (2020). Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. Nature Genetics, (3).

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. / Rodriguez-Martin, Bernardo; Alvarez, Eva G.; Baez-Ortega, Adrian; Zamora, Jorge; Supek, Fran; Demeulemeester, Jonas; Santamarina, Martin; Ju, Young Seok; Temes, Javier; Garcia-Souto, Daniel; Detering, Harald; Li, Yilong; Rodriguez-Castro, Jorge; Dueso-Barroso, Ana; Bruzos, Alicia L.; Dentro, Stefan C.; Blanco, Miguel G.; Contino, Gianmarco; Ardeljan, Daniel; Tojo, Marta; Roberts, Nicola D.; Zumalave, Sonia; Edwards, Paul A. W.; Weischenfeldt, Joachim; Puiggròs, Montserrat; Chong, Zechen; Chen, Ken; Lee, Eunjung Alice; Wala, Jeremiah A.; Raine, Keiran; Butler, Adam; Waszak, Sebastian M.; Navarro, Fabio C. P.; Schumacher, Steven E.; Monlong, Jean; Maura, Francesco; Bolli, Niccolo; Bourque, Guillaume; Gerstein, Mark; Park, Peter J.; Wedge, David C.; Beroukhim, Rameen; Torrents, David; Korbel, Jan O.; Martincorena, Inigo; Fitzgerald, Rebecca C.; Van Loo, Peter; Kazazian, Haig H.; Burns, Kathleen H.; Campbell, Peter J.; Tubio, Jose M. C.

In: Nature Genetics, No. 3, 01.03.2020.

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

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, PAW, Weischenfeldt, J, Puiggròs, M, Chong, Z, Chen, K, Lee, EA, Wala, JA, Raine, K, 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 2020, 'Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.', Nature Genetics, no. 3.

Rodriguez-Martin, Bernardo ; Alvarez, Eva G. ; Baez-Ortega, Adrian ; Zamora, Jorge ; Supek, Fran ; Demeulemeester, Jonas ; Santamarina, Martin ; Ju, Young Seok ; Temes, Javier ; Garcia-Souto, Daniel ; Detering, Harald ; Li, Yilong ; Rodriguez-Castro, Jorge ; Dueso-Barroso, Ana ; Bruzos, Alicia L. ; Dentro, Stefan C. ; Blanco, Miguel G. ; Contino, Gianmarco ; Ardeljan, Daniel ; Tojo, Marta ; Roberts, Nicola D. ; Zumalave, Sonia ; Edwards, Paul A. W. ; Weischenfeldt, Joachim ; Puiggròs, Montserrat ; Chong, Zechen ; Chen, Ken ; Lee, Eunjung Alice ; Wala, Jeremiah A. ; Raine, Keiran ; Butler, Adam ; Waszak, Sebastian M. ; Navarro, Fabio C. P. ; Schumacher, Steven E. ; Monlong, Jean ; Maura, Francesco ; Bolli, Niccolo ; Bourque, Guillaume ; Gerstein, Mark ; Park, Peter J. ; Wedge, David C. ; Beroukhim, Rameen ; Torrents, David ; Korbel, Jan O. ; Martincorena, Inigo ; Fitzgerald, Rebecca C. ; Van Loo, Peter ; Kazazian, Haig H. ; Burns, Kathleen H. ; Campbell, Peter J. ; Tubio, Jose M. C. / Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. In: Nature Genetics. 2020 ; No. 3.

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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 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.",

author = "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. W.} and Joachim Weischenfeldt and Montserrat Puiggr{\`o}s and Zechen Chong and Ken Chen and Lee, {Eunjung Alice} and Wala, {Jeremiah A.} and Keiran Raine 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 Inigo 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.}",

year = "2020",

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journal = "Nature Genetics",

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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. W.

AU - Weischenfeldt, Joachim

AU - Puiggròs, Montserrat

AU - Chong, Zechen

AU - Chen, Ken

AU - Lee, Eunjung Alice

AU - Wala, Jeremiah A.

AU - Raine, Keiran

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, Inigo

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.

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 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.

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 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.

M3 - Article

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -

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

Abstract

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