Landscape of somatic mutations in 560 breast cancer whole-genome sequences

Serena Nik-Zainal; Helen Davies; Johan Staaf; Manasa Ramakrishna; Dominik Glodzik; Xueqing Zou; Inigo Martincorena; Ludmil B Alexandrov; Sancha Martin; David C Wedge; Peter Van Loo; Young Seok Ju; Marcel Smid; Arie B Brinkman; Sandro Morganella; Miriam R Aure; Ole Christian Lingjærde; Anita Langerød; Markus Ringnér; Sung-Min Ahn; Sandrine Boyault; Jane E Brock; Annegien Broeks; Adam Butler; Christine Desmedt; Luc Dirix; Serge Dronov; Aquila Fatima; John A Foekens; Moritz Gerstung; Gerrit K J Hooijer; Se Jin Jang; David R Jones; Hyung-Yong Kim; Tari A King; Savitri Krishnamurthy; Hee Jin Lee; Jeong-Yeon Lee; Yilong Li; Stuart McLaren; Andrew Menzies; Ville Mustonen; Sarah O'Meara; Iris Pauporté; Xavier Pivot; Colin A Purdie; Keiran Raine; Kamna Ramakrishnan; F Germán Rodríguez-González; Gilles Romieu; Anieta M Sieuwerts; Peter T Simpson; Rebecca Shepherd; Lucy Stebbings; Olafur A Stefansson; Jon Teague; Stefania Tommasi; Isabelle Treilleux; Gert G Van den Eynden; Peter Vermeulen; Anne Vincent-Salomon; Lucy Yates; Carlos Caldas; Laura van't Veer; Andrew Tutt; Stian Knappskog; Benita Kiat Tee Tan; Jos Jonkers; Åke Borg; Naoto T Ueno; Christos Sotiriou; Alain Viari; P Andrew Futreal; Peter J Campbell; Paul N Span; Steven Van Laere; Sunil R Lakhani; Jorunn E Eyfjord; Alastair M Thompson; Ewan Birney; Hendrik G Stunnenberg; Marc J van de Vijver; John W M Martens; Anne-Lise Børresen-Dale; Andrea L Richardson; Gu Kong; Gilles Thomas; Michael R Stratton

doi:10.1038/nature17676

Standard

Landscape of somatic mutations in 560 breast cancer whole-genome sequences. / Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B; Martin, Sancha; Wedge, David C; Van Loo, Peter; Ju, Young Seok; Smid, Marcel; Brinkman, Arie B; Morganella, Sandro; Aure, Miriam R; Lingjærde, Ole Christian; Langerød, Anita; Ringnér, Markus; Ahn, Sung-Min; Boyault, Sandrine; Brock, Jane E; Broeks, Annegien; Butler, Adam; Desmedt, Christine; Dirix, Luc; Dronov, Serge; Fatima, Aquila; Foekens, John A; Gerstung, Moritz; Hooijer, Gerrit K J; Jang, Se Jin; Jones, David R; Kim, Hyung-Yong; King, Tari A; Krishnamurthy, Savitri; Lee, Hee Jin; Lee, Jeong-Yeon; Li, Yilong; McLaren, Stuart; Menzies, Andrew; Mustonen, Ville; O'Meara, Sarah; Pauporté, Iris; Pivot, Xavier; Purdie, Colin A; Raine, Keiran; Ramakrishnan, Kamna; Rodríguez-González, F Germán; Romieu, Gilles; Sieuwerts, Anieta M; Simpson, Peter T; Shepherd, Rebecca; Stebbings, Lucy; Stefansson, Olafur A; Teague, Jon; Tommasi, Stefania; Treilleux, Isabelle; Van den Eynden, Gert G; Vermeulen, Peter; Vincent-Salomon, Anne; Yates, Lucy; Caldas, Carlos; van't Veer, Laura; Tutt, Andrew; Knappskog, Stian; Tan, Benita Kiat Tee; Jonkers, Jos; Borg, Åke; Ueno, Naoto T; Sotiriou, Christos; Viari, Alain; Futreal, P Andrew; Campbell, Peter J; Span, Paul N; Van Laere, Steven; Lakhani, Sunil R; Eyfjord, Jorunn E; Thompson, Alastair M; Birney, Ewan; Stunnenberg, Hendrik G; van de Vijver, Marc J; Martens, John W M; Børresen-Dale, Anne-Lise; Richardson, Andrea L; Kong, Gu; Thomas, Gilles; Stratton, Michael R.

In: Nature, Vol. 534, No. 7605, 02.06.2016, p. 47-54.

Research output: Contribution to journal › Article

Harvard

Nik-Zainal, S, Davies, H, Staaf, J, Ramakrishna, M, Glodzik, D, Zou, X, Martincorena, I, Alexandrov, LB, Martin, S, Wedge, DC, Van Loo, P, Ju, YS, Smid, M, Brinkman, AB, Morganella, S, Aure, MR, Lingjærde, OC, Langerød, A, Ringnér, M, Ahn, S-M, Boyault, S, Brock, JE, Broeks, A, Butler, A, Desmedt, C, Dirix, L, Dronov, S, Fatima, A, Foekens, JA, Gerstung, M, Hooijer, GKJ, Jang, SJ, Jones, DR, Kim, H-Y, King, TA, Krishnamurthy, S, Lee, HJ, Lee, J-Y, Li, Y, McLaren, S, Menzies, A, Mustonen, V, O'Meara, S, Pauporté, I, Pivot, X, Purdie, CA, Raine, K, Ramakrishnan, K, Rodríguez-González, FG, Romieu, G, Sieuwerts, AM, Simpson, PT, Shepherd, R, Stebbings, L, Stefansson, OA, Teague, J, Tommasi, S, Treilleux, I, Van den Eynden, GG, Vermeulen, P, Vincent-Salomon, A, Yates, L, Caldas, C, van't Veer, L, Tutt, A, Knappskog, S, Tan, BKT, Jonkers, J, Borg, Å, Ueno, NT, Sotiriou, C, Viari, A, Futreal, PA, Campbell, PJ, Span, PN, Van Laere, S, Lakhani, SR, Eyfjord, JE, Thompson, AM, Birney, E, Stunnenberg, HG, van de Vijver, MJ, Martens, JWM, Børresen-Dale, A-L, Richardson, AL, Kong, G, Thomas, G & Stratton, MR 2016, 'Landscape of somatic mutations in 560 breast cancer whole-genome sequences', Nature, vol. 534, no. 7605, pp. 47-54. https://doi.org/10.1038/nature17676

APA

Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L. B., Martin, S., Wedge, D. C., Van Loo, P., Ju, Y. S., Smid, M., Brinkman, A. B., Morganella, S., Aure, M. R., Lingjærde, O. C., Langerød, A., Ringnér, M., ... Stratton, M. R. (2016). Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature, 534(7605), 47-54. https://doi.org/10.1038/nature17676

CBE

Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, Martincorena I, Alexandrov LB, Martin S, Wedge DC, Van Loo P, Ju YS, Smid M, Brinkman AB, Morganella S, Aure MR, Lingjærde OC, Langerød A, Ringnér M, Ahn S-M, Boyault S, Brock JE, Broeks A, Butler A, Desmedt C, Dirix L, Dronov S, Fatima A, Foekens JA, Gerstung M, Hooijer GKJ, Jang SJ, Jones DR, Kim H-Y, King TA, Krishnamurthy S, Lee HJ, Lee J-Y, Li Y, McLaren S, Menzies A, Mustonen V, O'Meara S, Pauporté I, Pivot X, Purdie CA, Raine K, Ramakrishnan K, Rodríguez-González FG, Romieu G, Sieuwerts AM, Simpson PT, Shepherd R, Stebbings L, Stefansson OA, Teague J, Tommasi S, Treilleux I, Van den Eynden GG, Vermeulen P, Vincent-Salomon A, Yates L, Caldas C, van't Veer L, Tutt A, Knappskog S, Tan BKT, Jonkers J, Borg Å, Ueno NT, Sotiriou C, Viari A, Futreal PA, Campbell PJ, Span PN, Van Laere S, Lakhani SR, Eyfjord JE, Thompson AM, Birney E, Stunnenberg HG, van de Vijver MJ, Martens JWM, Børresen-Dale A-L, Richardson AL, Kong G, Thomas G, Stratton MR. 2016. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 534(7605):47-54. https://doi.org/10.1038/nature17676

MLA

Nik-Zainal, Serena et al. "Landscape of somatic mutations in 560 breast cancer whole-genome sequences". Nature. 2016, 534(7605). 47-54. https://doi.org/10.1038/nature17676

Vancouver

Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 2016 Jun 2;534(7605):47-54. https://doi.org/10.1038/nature17676

Author

Nik-Zainal, Serena ; Davies, Helen ; Staaf, Johan ; Ramakrishna, Manasa ; Glodzik, Dominik ; Zou, Xueqing ; Martincorena, Inigo ; Alexandrov, Ludmil B ; Martin, Sancha ; Wedge, David C ; Van Loo, Peter ; Ju, Young Seok ; Smid, Marcel ; Brinkman, Arie B ; Morganella, Sandro ; Aure, Miriam R ; Lingjærde, Ole Christian ; Langerød, Anita ; Ringnér, Markus ; Ahn, Sung-Min ; Boyault, Sandrine ; Brock, Jane E ; Broeks, Annegien ; Butler, Adam ; Desmedt, Christine ; Dirix, Luc ; Dronov, Serge ; Fatima, Aquila ; Foekens, John A ; Gerstung, Moritz ; Hooijer, Gerrit K J ; Jang, Se Jin ; Jones, David R ; Kim, Hyung-Yong ; King, Tari A ; Krishnamurthy, Savitri ; Lee, Hee Jin ; Lee, Jeong-Yeon ; Li, Yilong ; McLaren, Stuart ; Menzies, Andrew ; Mustonen, Ville ; O'Meara, Sarah ; Pauporté, Iris ; Pivot, Xavier ; Purdie, Colin A ; Raine, Keiran ; Ramakrishnan, Kamna ; Rodríguez-González, F Germán ; Romieu, Gilles ; Sieuwerts, Anieta M ; Simpson, Peter T ; Shepherd, Rebecca ; Stebbings, Lucy ; Stefansson, Olafur A ; Teague, Jon ; Tommasi, Stefania ; Treilleux, Isabelle ; Van den Eynden, Gert G ; Vermeulen, Peter ; Vincent-Salomon, Anne ; Yates, Lucy ; Caldas, Carlos ; van't Veer, Laura ; Tutt, Andrew ; Knappskog, Stian ; Tan, Benita Kiat Tee ; Jonkers, Jos ; Borg, Åke ; Ueno, Naoto T ; Sotiriou, Christos ; Viari, Alain ; Futreal, P Andrew ; Campbell, Peter J ; Span, Paul N ; Van Laere, Steven ; Lakhani, Sunil R ; Eyfjord, Jorunn E ; Thompson, Alastair M ; Birney, Ewan ; Stunnenberg, Hendrik G ; van de Vijver, Marc J ; Martens, John W M ; Børresen-Dale, Anne-Lise ; Richardson, Andrea L ; Kong, Gu ; Thomas, Gilles ; Stratton, Michael R. / Landscape of somatic mutations in 560 breast cancer whole-genome sequences. In: Nature. 2016 ; Vol. 534, No. 7605. pp. 47-54.

RIS

TY - JOUR

T1 - Landscape of somatic mutations in 560 breast cancer whole-genome sequences

AU - Nik-Zainal, Serena

AU - Davies, Helen

AU - Staaf, Johan

AU - Ramakrishna, Manasa

AU - Glodzik, Dominik

AU - Zou, Xueqing

AU - Martincorena, Inigo

AU - Alexandrov, Ludmil B

AU - Martin, Sancha

AU - Wedge, David C

AU - Van Loo, Peter

AU - Ju, Young Seok

AU - Smid, Marcel

AU - Brinkman, Arie B

AU - Morganella, Sandro

AU - Aure, Miriam R

AU - Lingjærde, Ole Christian

AU - Langerød, Anita

AU - Ringnér, Markus

AU - Ahn, Sung-Min

AU - Boyault, Sandrine

AU - Brock, Jane E

AU - Broeks, Annegien

AU - Butler, Adam

AU - Desmedt, Christine

AU - Dirix, Luc

AU - Dronov, Serge

AU - Fatima, Aquila

AU - Foekens, John A

AU - Gerstung, Moritz

AU - Hooijer, Gerrit K J

AU - Jang, Se Jin

AU - Jones, David R

AU - Kim, Hyung-Yong

AU - King, Tari A

AU - Krishnamurthy, Savitri

AU - Lee, Hee Jin

AU - Lee, Jeong-Yeon

AU - Li, Yilong

AU - McLaren, Stuart

AU - Menzies, Andrew

AU - Mustonen, Ville

AU - O'Meara, Sarah

AU - Pauporté, Iris

AU - Pivot, Xavier

AU - Purdie, Colin A

AU - Raine, Keiran

AU - Ramakrishnan, Kamna

AU - Rodríguez-González, F Germán

AU - Romieu, Gilles

AU - Sieuwerts, Anieta M

AU - Simpson, Peter T

AU - Shepherd, Rebecca

AU - Stebbings, Lucy

AU - Stefansson, Olafur A

AU - Teague, Jon

AU - Tommasi, Stefania

AU - Treilleux, Isabelle

AU - Van den Eynden, Gert G

AU - Vermeulen, Peter

AU - Vincent-Salomon, Anne

AU - Yates, Lucy

AU - Caldas, Carlos

AU - van't Veer, Laura

AU - Tutt, Andrew

AU - Knappskog, Stian

AU - Tan, Benita Kiat Tee

AU - Jonkers, Jos

AU - Borg, Åke

AU - Ueno, Naoto T

AU - Sotiriou, Christos

AU - Viari, Alain

AU - Futreal, P Andrew

AU - Campbell, Peter J

AU - Span, Paul N

AU - Van Laere, Steven

AU - Lakhani, Sunil R

AU - Eyfjord, Jorunn E

AU - Thompson, Alastair M

AU - Birney, Ewan

AU - Stunnenberg, Hendrik G

AU - van de Vijver, Marc J

AU - Martens, John W M

AU - Børresen-Dale, Anne-Lise

AU - Richardson, Andrea L

AU - Kong, Gu

AU - Thomas, Gilles

AU - Stratton, Michael R

PY - 2016/6/2

Y1 - 2016/6/2

N2 - We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

AB - We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

KW - Breast Neoplasms

KW - Cohort Studies

KW - DNA Mutational Analysis

KW - DNA Replication

KW - DNA, Neoplasm

KW - Female

KW - Genes, BRCA1

KW - Genes, BRCA2

KW - Genome, Human

KW - Genomics

KW - Humans

KW - Male

KW - Mutagenesis

KW - Mutation

KW - Mutation Rate

KW - Oncogenes

KW - Recombinational DNA Repair

U2 - 10.1038/nature17676

DO - 10.1038/nature17676

M3 - Article

C2 - 27135926

VL - 534

SP - 47

EP - 54

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7605

ER -