Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

PCAWG-Structural Variation Working Group; PCAWG Consortium; Isidro Cortés-Ciriano; Jake June Koo Lee; Ruibin Xi; Dhawal Jain; Youngsook L. Jung; Lixing Yang; Dmitry Gordenin; Leszek J. Klimczak; Cheng Zhong Zhang; David S. Pellman; Kadir C. Akdemir; Eva G. Alvarez; Adrian Baez-Ortega; Rameen Beroukhim; Paul C. Boutros; David D.L. Bowtell; Benedikt Brors; Kathleen H. Burns; Peter J. Campbell; Kin Chan; Ken Chen; Isidro Cortés-Ciriano; Ana Dueso-Barroso; Andrew J. Dunford; Paul A. Edwards; Xavier Estivill; Dariush Etemadmoghadam; Lars Feuerbach; J. Lynn Fink; Milana Frenkel-Morgenstern; Dale W. Garsed; Mark Gerstein; Dmitry A. Gordenin; David Haan; James E. Haber; Julian M. Hess; Barbara Hutter; Marcin Imielinski; David T.W. Jones; Young Seok Ju; Marat D. Kazanov; Youngil Koh; Jan O. Korbel; Kiran Kumar; Eunjung Alice Lee; Yilong Li; Andy G. Lynch; Geoff Macintyre; Florian Markowetz; Iñigo Martincorena; Alexander Martinez-Fundichely; Satoru Miyano; Hidewaki Nakagawa; Fabio C.P. Navarro; Stephan Ossowski; John V. Pearson; Montserrat Puiggròs; Karsten Rippe; Nicola D. Roberts; Steven A. Roberts; Bernardo Rodriguez-Martin; Steven E. Schumacher; Ralph Scully; Mark Shackleton; Nikos Sidiropoulos; Lina Sieverling; Chip Stewart; David Torrents; Jose M.C. Tubio; Izar Villasante; Nicola Waddell; Jeremiah A. Wala; Joachim Weischenfeldt; Lixing Yang; Xiaotong Yao; Sung Soo Yoon; Jorge Zamora; Peter J. Park; Lauri A. Aaltonen; Federico Abascal; Adam Abeshouse; Hiroyuki Aburatani; David J. Adams; Nishant Agrawal; Keun Soo Ahn; Sung Min Ahn; Hiroshi Aikata; Rehan Akbani; Kadir C. Akdemir; Hikmat Al-Ahmadie; Sultan T. Al-Sedairy; Fatima Al-Shahrour; Malik Alawi; Monique Albert; Kenneth Aldape; Ludmil B. Alexandrov; Adrian Ally; Kathryn Alsop; Eva G. Alvarez; 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; Adrian Baez-Ortega; 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; Lori Boice; Giada Bonizzato; Johann S. De Bono; Arnoud Boot; Moiz S. Bootwalla; Ake Borg; Arndt Borkhardt; Keith A. Boroevich; Ivan Borozan; Christoph Borst; Marcus Bosenberg; Mattia Bosio; Jacqueline Boultwood; Guillaume Bourque; Paul C. Boutros; G. Steven Bova; David T. Bowen; Li Ding; Lucinda A. Fulton; Robert S. Fulton; Ramaswamy Govindan; Reyka Jayasinghe; Tim Ley; Christopher A. Miller; Francesc Muyas; Johannes Werner

doi:10.1038/s41588-019-0576-7

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

PCAWG-Structural Variation Working Group, PCAWG Consortium, Isidro Cortés-Ciriano, Jake June Koo Lee, Ruibin Xi, Dhawal Jain, Youngsook L. Jung, Lixing Yang, Dmitry Gordenin, Leszek J. Klimczak, Cheng Zhong Zhang, David S. Pellman, Kadir C. Akdemir, Eva G. Alvarez, Adrian Baez-Ortega, Rameen Beroukhim, Paul C. Boutros, David D.L. Bowtell, Benedikt Brors, Kathleen H. BurnsPeter J. Campbell, Kin Chan, Ken Chen, Isidro Cortés-Ciriano, Ana Dueso-Barroso, Andrew J. Dunford, Paul A. Edwards, Xavier Estivill, Dariush Etemadmoghadam, Lars Feuerbach, J. Lynn Fink, Milana Frenkel-Morgenstern, Dale W. Garsed, Mark Gerstein, Dmitry A. Gordenin, David Haan, James E. Haber, Julian M. Hess, Barbara Hutter, Marcin Imielinski, David T.W. Jones, Young Seok Ju, Marat D. Kazanov, Youngil Koh, Jan O. Korbel, Kiran Kumar, Eunjung Alice Lee, Yilong Li, Andy G. Lynch, Geoff Macintyre, Florian Markowetz, Iñigo Martincorena, Alexander Martinez-Fundichely, Satoru Miyano, Hidewaki Nakagawa, Fabio C.P. Navarro, Stephan Ossowski, John V. Pearson, Montserrat Puiggròs, Karsten Rippe, Nicola D. Roberts, Steven A. Roberts, Bernardo Rodriguez-Martin, Steven E. Schumacher, Ralph Scully, Mark Shackleton, Nikos Sidiropoulos, Lina Sieverling, Chip Stewart, David Torrents, Jose M.C. Tubio, Izar Villasante, Nicola Waddell, Jeremiah A. Wala, Joachim Weischenfeldt, Lixing Yang, Xiaotong Yao, Sung Soo Yoon, Jorge Zamora, Peter J. Park, Lauri A. Aaltonen, Federico Abascal, Adam Abeshouse, Hiroyuki Aburatani, David J. Adams, Nishant Agrawal, Keun Soo Ahn, Sung Min Ahn, Hiroshi Aikata, Rehan Akbani, Kadir C. Akdemir, Hikmat Al-Ahmadie, Sultan T. Al-Sedairy, Fatima Al-Shahrour, Malik Alawi, Monique Albert, Kenneth Aldape, Ludmil B. Alexandrov, Adrian Ally, Kathryn Alsop, Eva G. Alvarez, 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, Adrian Baez-Ortega, 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, Lori Boice, Giada Bonizzato, Johann S. De Bono, Arnoud Boot, Moiz S. Bootwalla, Ake Borg, Arndt Borkhardt, Keith A. Boroevich, Ivan Borozan, Christoph Borst, Marcus Bosenberg, Mattia Bosio, Jacqueline Boultwood, Guillaume Bourque, Paul C. Boutros, G. Steven Bova, David T. Bowen, Li Ding, Lucinda A. Fulton, Robert S. Fulton, Ramaswamy Govindan, Reyka Jayasinghe, Tim Ley, Christopher A. Miller, Francesc Muyas, Johannes Werner

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

414 Scopus citations

Abstract

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.

Original language	English
Pages (from-to)	331-341
Number of pages	11
Journal	Nature Genetics
Volume	52
Issue number	3
DOIs	https://doi.org/10.1038/s41588-019-0576-7
State	Published - Mar 1 2020

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10.1038/s41588-019-0576-7

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PCAWG-Structural Variation Working Group, PCAWG Consortium, Cortés-Ciriano, I., Lee, J. J. K., Xi, R., Jain, D., Jung, Y. L., Yang, L., Gordenin, D., Klimczak, L. J., Zhang, C. Z., Pellman, D. S., Akdemir, K. C., Alvarez, E. G., Baez-Ortega, A., Beroukhim, R., Boutros, P. C., Bowtell, D. D. L., Brors, B., ... Werner, J. (2020). Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nature Genetics, 52(3), 331-341. https://doi.org/10.1038/s41588-019-0576-7

@article{655217886fcb4a3d86cfaadb371dfc45,

title = "Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing",

abstract = "Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.",

author = "{PCAWG-Structural Variation Working Group} and {PCAWG Consortium} and Isidro Cort{\'e}s-Ciriano and Lee, {Jake June Koo} and Ruibin Xi and Dhawal Jain and Jung, {Youngsook L.} and Lixing Yang and Dmitry Gordenin and Klimczak, {Leszek J.} and Zhang, {Cheng Zhong} and Pellman, {David S.} and Akdemir, {Kadir C.} and Alvarez, {Eva G.} and Adrian Baez-Ortega and Rameen Beroukhim and Boutros, {Paul C.} and Bowtell, {David D.L.} and Benedikt Brors and Burns, {Kathleen H.} and Campbell, {Peter J.} and Kin Chan and Ken Chen and Isidro Cort{\'e}s-Ciriano and Ana Dueso-Barroso and Dunford, {Andrew J.} and Edwards, {Paul A.} and Xavier Estivill and Dariush Etemadmoghadam and Lars Feuerbach and Fink, {J. Lynn} and Milana Frenkel-Morgenstern and Garsed, {Dale W.} and Mark Gerstein 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 Ju, {Young Seok} and Kazanov, {Marat D.} and Youngil Koh and Korbel, {Jan O.} and Kiran Kumar and Lee, {Eunjung Alice} and Yilong Li and Lynch, {Andy G.} and Geoff Macintyre and Florian Markowetz and I{\~n}igo Martincorena and Alexander Martinez-Fundichely and Satoru Miyano and Hidewaki Nakagawa and Navarro, {Fabio C.P.} and Stephan Ossowski and Pearson, {John V.} and Montserrat Puiggr{\`o}s and Karsten Rippe and Roberts, {Nicola D.} and Roberts, {Steven A.} and Bernardo Rodriguez-Martin and Schumacher, {Steven E.} and Ralph Scully and Mark Shackleton and Nikos Sidiropoulos and Lina Sieverling and Chip Stewart and David Torrents and Tubio, {Jose M.C.} and Izar Villasante and Nicola Waddell and Wala, {Jeremiah A.} and Joachim Weischenfeldt and Lixing Yang and Xiaotong Yao and Yoon, {Sung Soo} and Jorge Zamora and Park, {Peter J.} 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 Akdemir, {Kadir C.} 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 Alvarez, {Eva G.} 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 Adrian Baez-Ortega 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 Lori Boice and Giada Bonizzato and {De Bono}, {Johann S.} and Arnoud Boot and Bootwalla, {Moiz S.} and Ake Borg and Arndt Borkhardt and Boroevich, {Keith A.} and Ivan Borozan and Christoph Borst and Marcus Bosenberg and Mattia Bosio and Jacqueline Boultwood and Guillaume Bourque and Boutros, {Paul C.} and Bova, {G. Steven} and Bowen, {David T.} 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 Francesc Muyas and Johannes Werner",

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

year = "2020",

month = mar,

day = "1",

doi = "10.1038/s41588-019-0576-7",

language = "English",

volume = "52",

pages = "331--341",

journal = "Nature Genetics",

issn = "1061-4036",

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PCAWG-Structural Variation Working Group, PCAWG Consortium, Cortés-Ciriano, I, Lee, JJK, Xi, R, Jain, D, Jung, YL, Yang, L, Gordenin, D, Klimczak, LJ, Zhang, CZ, Pellman, DS, Akdemir, KC, Alvarez, EG, Baez-Ortega, A, Beroukhim, R, Boutros, PC, Bowtell, DDL, Brors, B, Burns, KH, Campbell, PJ, Chan, K, Chen, K, Cortés-Ciriano, I, Dueso-Barroso, A, Dunford, AJ, Edwards, PA, Estivill, X, Etemadmoghadam, D, Feuerbach, L, Fink, JL, Frenkel-Morgenstern, M, Garsed, DW, Gerstein, M, Gordenin, DA, Haan, D, Haber, JE, Hess, JM, Hutter, B, Imielinski, M, Jones, DTW, Ju, YS, Kazanov, MD, Koh, Y, Korbel, JO, Kumar, K, Lee, EA, Li, Y, Lynch, AG, Macintyre, G, Markowetz, F, Martincorena, I, Martinez-Fundichely, A, Miyano, S, Nakagawa, H, Navarro, FCP, Ossowski, S, Pearson, JV, Puiggròs, M, Rippe, K, Roberts, ND, Roberts, SA, Rodriguez-Martin, B, Schumacher, SE, Scully, R, Shackleton, M, Sidiropoulos, N, Sieverling, L, Stewart, C, Torrents, D, Tubio, JMC, Villasante, I, Waddell, N, Wala, JA, Weischenfeldt, J, Yang, L, Yao, X, Yoon, SS, Zamora, J, Park, PJ, Aaltonen, LA, Abascal, F, Abeshouse, A, Aburatani, H, Adams, DJ, Agrawal, N, Ahn, KS, Ahn, SM, Aikata, H, Akbani, R, Akdemir, KC, Al-Ahmadie, H, Al-Sedairy, ST, Al-Shahrour, F, Alawi, M, Albert, M, Aldape, K, Alexandrov, LB, Ally, A, Alsop, K, Alvarez, EG, 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, Baez-Ortega, A, 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, Boice, L, Bonizzato, G, De Bono, JS, Boot, A, Bootwalla, MS, Borg, A, Borkhardt, A, Boroevich, KA, Borozan, I, Borst, C, Bosenberg, M, Bosio, M, Boultwood, J, Bourque, G, Boutros, PC, Bova, GS, Bowen, DT, Ding, L , Fulton, LA , Fulton, RS , Govindan, R , Jayasinghe, R , Ley, T , Miller, CA , Muyas, F & Werner, J 2020, 'Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing', Nature Genetics, vol. 52, no. 3, pp. 331-341. https://doi.org/10.1038/s41588-019-0576-7

TY - JOUR

T1 - Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

AU - PCAWG-Structural Variation Working Group

AU - PCAWG Consortium

AU - Cortés-Ciriano, Isidro

AU - Lee, Jake June Koo

AU - Xi, Ruibin

AU - Jain, Dhawal

AU - Jung, Youngsook L.

AU - Yang, Lixing

AU - Gordenin, Dmitry

AU - Klimczak, Leszek J.

AU - Zhang, Cheng Zhong

AU - Pellman, David S.

AU - Akdemir, Kadir C.

AU - Alvarez, Eva G.

AU - Baez-Ortega, Adrian

AU - Beroukhim, Rameen

AU - Boutros, Paul C.

AU - Bowtell, David D.L.

AU - Brors, Benedikt

AU - Burns, Kathleen H.

AU - Campbell, Peter J.

AU - Chan, Kin

AU - Chen, Ken

AU - Cortés-Ciriano, Isidro

AU - Dueso-Barroso, Ana

AU - Dunford, Andrew J.

AU - Edwards, Paul A.

AU - Estivill, Xavier

AU - Etemadmoghadam, Dariush

AU - Feuerbach, Lars

AU - Fink, J. Lynn

AU - Frenkel-Morgenstern, Milana

AU - Garsed, Dale W.

AU - Gerstein, Mark

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 - Ju, Young Seok

AU - Kazanov, Marat D.

AU - Koh, Youngil

AU - Korbel, Jan O.

AU - Kumar, Kiran

AU - Lee, Eunjung Alice

AU - Li, Yilong

AU - Lynch, Andy G.

AU - Macintyre, Geoff

AU - Markowetz, Florian

AU - Martincorena, Iñigo

AU - Martinez-Fundichely, Alexander

AU - Miyano, Satoru

AU - Nakagawa, Hidewaki

AU - Navarro, Fabio C.P.

AU - Ossowski, Stephan

AU - Pearson, John V.

AU - Puiggròs, Montserrat

AU - Rippe, Karsten

AU - Roberts, Nicola D.

AU - Roberts, Steven A.

AU - Rodriguez-Martin, Bernardo

AU - Schumacher, Steven E.

AU - Scully, Ralph

AU - Shackleton, Mark

AU - Sidiropoulos, Nikos

AU - Sieverling, Lina

AU - Stewart, Chip

AU - Torrents, David

AU - Tubio, Jose M.C.

AU - Villasante, Izar

AU - Waddell, Nicola

AU - Wala, Jeremiah A.

AU - Weischenfeldt, Joachim

AU - Yang, Lixing

AU - Yao, Xiaotong

AU - Yoon, Sung Soo

AU - Zamora, Jorge

AU - Park, Peter J.

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 - Akdemir, Kadir C.

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 - Alvarez, Eva G.

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 - Baez-Ortega, Adrian

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 - Boice, Lori

AU - Bonizzato, Giada

AU - De Bono, Johann S.

AU - Boot, Arnoud

AU - Bootwalla, Moiz S.

AU - Borg, Ake

AU - Borkhardt, Arndt

AU - Boroevich, Keith A.

AU - Borozan, Ivan

AU - Borst, Christoph

AU - Bosenberg, Marcus

AU - Bosio, Mattia

AU - Boultwood, Jacqueline

AU - Bourque, Guillaume

AU - Boutros, Paul C.

AU - Bova, G. Steven

AU - Bowen, David T.

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 - Muyas, Francesc

AU - Werner, Johannes

PY - 2020/3/1

Y1 - 2020/3/1

N2 - Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.

AB - Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.

UR - http://www.scopus.com/inward/record.url?scp=85079044799&partnerID=8YFLogxK

U2 - 10.1038/s41588-019-0576-7

DO - 10.1038/s41588-019-0576-7

M3 - Article

C2 - 32025003

AN - SCOPUS:85079044799

SN - 1061-4036

VL - 52

SP - 331

EP - 341

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

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