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. 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; PCAWG Structural Variation Working Group; Peter J. Campbell; Jose M.C. Tubio; PCAWG Consortium; Neil Merrett; et al.

doi:10.1038/s41588-019-0562-0

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. 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, PCAWG Structural Variation Working Group, Peter J. Campbell, Jose M.C. Tubio, PCAWG Consortium, Neil Merrett, et al.

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 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.

There is an author correction to the original article - https://doi.org/10.1038/s41588-023-01319-9

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
Publication status	Published - Feb 2020
Externally published	Yes

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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., ... et al. (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{548eb6e119fa4eaca2385fd91ac9a688,

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. There is an author correction to the original article - https://doi.org/10.1038/s41588-023-01319-9",

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.} 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 {PCAWG Structural Variation Working Group} and Campbell, {Peter J.} and Tubio, {Jose M.C.} and {PCAWG Consortium} and Neil Merrett and {et al.}",

year = "2020",

month = feb,

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

language = "English",

volume = "52",

pages = "306--319",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

}

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, PCAWG Structural Variation Working Group, Campbell, PJ, Tubio, JMC, PCAWG Consortium, , Merrett, N & et al. 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 - 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 - PCAWG Structural Variation Working Group,

AU - Campbell, Peter J.

AU - Tubio, Jose M.C.

AU - PCAWG Consortium,

AU - Merrett, Neil

AU - et al.,

PY - 2020/2

Y1 - 2020/2

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. There is an author correction to the original article - https://doi.org/10.1038/s41588-023-01319-9

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. There is an author correction to the original article - https://doi.org/10.1038/s41588-023-01319-9

U2 - 10.1038/s41588-019-0562-0

DO - 10.1038/s41588-019-0562-0

M3 - Article

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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