Signatures of mutational processes in human cancer

被引：7548

作者：

Alexandrov, Ludmil B. ^{[1
]}

Nik-Zainal, Serena ^{[1
,2
]}

Wedge, David C. ^{[1
]}

Aparicio, Samuel A. J. R. ^{[3
,4
,5
]}

Behjati, Sam ^{[1
,6
]}

Biankin, Andrew V. ^{[7
,8
,9
,10
,11
,12
]}

Bignell, Graham R. ^{[1
]}

Bolli, Niccolo ^{[1
,13
,14
]}

Borg, Ake ^{[15
]}

Borresen-Dale, Anne-Lise ^{[16
,17
]}

Boyault, Sandrine ^{[18
]}

Burkhardt, Birgit ^{[19
,20
,21
,22
]}

Butler, Adam P. ^{[1
]}

Caldas, Carlos ^{[23
]}

Davies, Helen R. ^{[1
]}

Desmedt, Christine ^{[24
]}

Eils, Roland ^{[25
]}

Eyfjord, Jorunn Erla ^{[26
]}

Foekens, John A. ^{[27
]}

Greaves, Mel ^{[28
]}

Hosoda, Fumie ^{[29
]}

Hutter, Barbara ^{[25
]}

Ilicic, Tomislav ^{[1
]}

Imbeaud, Sandrine ^{[30
,31
]}

Imielinsk, Marcin ^{[32
]}

Jaeger, Natalie ^{[25
]}

Jones, David T. W. ^{[33
]}

Jones, David ^{[1
]}

Knappskog, Stian ^{[34
,35
]}

Kool, Marcel ^{[33
]}

Lakhani, Sunil R. ^{[36
]}

Lopez-Otin, Carlos ^{[37
]}

Martin, Sancha ^{[1
]}

Munshi, Nikhil C. ^{[38
,39
]}

Nakamura, Hiromi ^{[29
]}

Northcott, Paul A. ^{[33
]}

Pajic, Marina ^{[7
]}

Papaemmanuil, Elli ^{[1
]}

Paradiso, Angelo ^{[40
]}

Pearson, John V. ^{[41
]}

Puente, Xose S. ^{[37
]}

Raine, Keiran ^{[1
]}

Ramakrishna, Manasa ^{[1
]}

Richardson, Andrea L. ^{[42
,43
,44
]}

Richter, Julia ^{[45
]}

Rosenstiel, Philip ^{[46
]}

Schlesner, Matthias ^{[25
]}

Schumacher, Ton N. ^{[47
]}

Span, Paul N. ^{[48
,49
]}

Teague, Jon W. ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England

[2] Addenbrookes Hosp NHS Trust, Dept Med Genet, Cambridge CB2 0QQ, England

[3] BC Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada

[4] BC Canc Agcy, Michael Smith Genome Sci Ctr, Ctr Translat & Appl Genom, Vancouver, BC V5Z 1L3, Canada

[5] Univ British Columbia, Dept Pathol, Vancouver, BC V6T 2B5, Canada

[6] Univ Cambridge, Dept Paediat, Cambridge CB2 2XY, England

[7] Univ Glasgow, Wolfson Wohl Canc Res Ctr, Inst Canc Sci, Glasgow G61 1BD, Lanark, Scotland

[8] Glasgow Royal Infirm, West Scotland Pancreat Unit, Glasgow G4 0SF, Lanark, Scotland

[9] Kinghorn Canc Ctr, Darlinghurst, NSW, Australia

[10] Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia

[11] Bankstown Hosp, Dept Surg, Sydney, NSW 2200, Australia

[12] Univ New S Wales, South Western Sydney Clin Sch, Fac Med, Liverpool, NSW 2170, Australia

[13] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 0QQ, England

[14] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England

[15] Lund Univ, Dept Oncol, SE-22185 Lund, Sweden

[16] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Genet, Inst Canc Res, N-0310 Oslo, Norway

[17] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0310 Oslo, Norway

[18] Ctr Leon Berard, Plateforme Bioinformat Synergie Lyon Canc, F-69373 Lyon 08, France

[19] Univ Childrens Hosp, NHL BFM Study Ctr, D-48149 Munster, Germany

[20] Univ Childrens Hosp, Dept Pediat Hematol & Oncol, D-48149 Munster, Germany

[21] Univ Childrens Hosp, NHL BFM Study Ctr, D-35392 Giessen, Germany

[22] Univ Childrens Hosp, Dept Pediat Hematol & Oncol, D-35392 Giessen, Germany

[23] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England

[24] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab BCTL, B-1000 Brussels, Belgium

[25] German Canc Res Ctr, Dept Theoret Bioinformat B080, D-69120 Heidelberg, Germany

[26] Univ Iceland, Canc Res Lab, Fac Med, Biomed Ctr, IS-101 Reykjavik, Iceland

[27] Erasmus MC Canc Inst, Dept Med Oncol, NL-3015 CE Rotterdam, Netherlands

[28] Inst Canc Res, Dept Haematooncol, Sutton SM2 5NG, Surrey, England

[29] Natl Canc Ctr, Res Inst, Div Canc Genom, Chuo Ku, Tokyo 1040045, Japan

[30] IUH, INSERM, UMR 674, F-75475 Paris, France

[31] Univ Paris 05, Sorbonne Paris Cite, Fac Med, F-75006 Paris, France

[32] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA

[33] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany

[34] Univ Bergen, Dept Clin Sci, Sect Oncol, N-5020 Bergen, Norway

[35] Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway

[36] Univ Queensland, Royal Brisbane & Womens Hosp, Clin Res Ctr, Sch Med & Pathol Queensland, Brisbane, Qld 4029, Australia

[37] Univ Oviedo, IUOPA, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain

[38] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Dis Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA

[39] Boston Vet Adm Healthcare Syst, West Roxbury, MA 02132 USA

[40] Natl Canc Inst, Clin Expt Oncol Lab, I-70126 Bari, Italy

[41] Univ Queensland, Queensland Ctr Med Genom, Inst Mol Biosci, Brisbane, Qld 4072, Australia

[42] Dana Farber Canc Inst, Boston, MA 02215 USA

[43] Harvard Univ, Sch Med, Boston, MA 02115 USA

[44] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[45] Univ Kiel, Inst Human Genet, D-24118 Kiel, Germany

[46] Univ Kiel, Inst Clin Mol Biol, D-24118 Kiel, Germany

[47] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands

[48] Radboud Univ Nijmegen, Med Ctr, Dept Radiat Oncol, NL-6500 HB Nijmegen, Netherlands

[49] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, NL-6500 HB Nijmegen, Netherlands

[50] Kings Coll London, Sch Med, Breakthrough Breast Canc Res Unit, London SW3 6JB, England

来源：

NATURE | 2013年 / 500卷 / 7463期

基金：

英国惠康基金;

关键词：

RECURRENT MUTATIONS; SOMATIC MUTATIONS; GENETIC LANDSCAPE; FREQUENT MUTATION; DRIVER MUTATIONS; MISMATCH REPAIR; EXOME; REVEALS; ADENOCARCINOMA; INSTABILITY;

D O I：

10.1038/nature12477

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.

引用

页码：415 / +

页数：10

共 64 条

[1]

Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1 [J].

Agrawal, Nishant ;

Frederick, Mitchell J. ;

Pickering, Curtis R. ;

Bettegowda, Chetan ;

Chang, Kyle ;

Li, Ryan J. ;

Fakhry, Carole ;

Xie, Tong-Xin ;

Zhang, Jiexin ;

Wang, Jing ;

Zhang, Nianxiang ;

El-Naggar, Adel K. ;

Jasser, Samar A. ;

Weinstein, John N. ;

Trevino, Lisa ;

Drummond, Jennifer A. ;

Muzny, Donna M. ;

Wu, Yuanqing ;

Wood, Laura D. ;

Hruban, Ralph H. ;

Westra, William H. ;

Koch, Wayne M. ;

Califano, Joseph A. ;

Gibbs, Richard A. ;

Sidransky, David ;

Vogelstein, Bert ;

Velculescu, Victor E. ;

Papadopoulos, Nickolas ;

Wheeler, David A. ;

Kinzler, Kenneth W. ;

Myers, Jeffrey N. .

SCIENCE, 2011, 333 (6046) :1154-1157

[2]

Deciphering Signatures of Mutational Processes Operative in Human Cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Campbell, Peter J. ;

Stratton, Michael R. .

CELL REPORTS, 2013, 3 (01) :246-259

[3]

An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[4]

Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer [J].

Barbieri, Christopher E. ;

Baca, Sylvan C. ;

Lawrence, Michael S. ;

Demichelis, Francesca ;

Blattner, Mirjam ;

Theurillat, Jean-Philippe ;

White, Thomas A. ;

Stojanov, Petar ;

Van Allen, Eliezer ;

Stransky, Nicolas ;

Nickerson, Elizabeth ;

Chae, Sung-Suk ;

Boysen, Gunther ;

Auclair, Daniel ;

Onofrio, Robert C. ;

Park, Kyung ;

Kitabayashi, Naoki ;

MacDonald, Theresa Y. ;

Sheikh, Karen ;

Vuong, Terry ;

Guiducci, Candace ;

Cibulskis, Kristian ;

Sivachenko, Andrey ;

Carter, Scott L. ;

Saksena, Gordon ;

Voet, Douglas ;

Hussain, Wasay M. ;

Ramos, Alex H. ;

Winckler, Wendy ;

Redman, Michelle C. ;

Ardlie, Kristin ;

Tewari, Ashutosh K. ;

Mosquera, Juan Miguel ;

Rupp, Niels ;

Wild, Peter J. ;

Moch, Holger ;

Morrissey, Colm ;

Nelson, Peter S. ;

Kantoff, Philip W. ;

Gabriel, Stacey B. ;

Golub, Todd R. ;

Meyerson, Matthew ;

Lander, Eric S. ;

Getz, Gad ;

Rubin, Mark A. ;

Garraway, Levi A. .

NATURE GENETICS, 2012, 44 (06) :685-U107

[5]

Comparison of the Agilent, ROMA/NimbleGen and Illumina platforms for classification of copy number alterations in human breast tumors [J].

Baumbusch, L. O. ;

Aaroe, J. ;

Johansen, F. E. ;

Hicks, J. ;

Sun, H. ;

Bruhn, L. ;

Gunderson, K. ;

Naume, B. ;

Kristensen, V. N. ;

Liestol, K. ;

Borresen-Dale, A-L ;

Lingjaerde, O. C. .

BMC GENOMICS, 2008, 9 (1)

[6]

Melanoma genome sequencing reveals frequent PREX2 mutations [J].

Berger, Michael F. ;

Hodis, Eran ;

Heffernan, Timothy P. ;

Deribe, Yonathan Lissanu ;

Lawrence, Michael S. ;

Protopopov, Alexei ;

Ivanova, Elena ;

Watson, Ian R. ;

Nickerson, Elizabeth ;

Ghosh, Papia ;

Zhang, Hailei ;

Zeid, Rhamy ;

Ren, Xiaojia ;

Cibulskis, Kristian ;

Sivachenko, Andrey Y. ;

Wagle, Nikhil ;

Sucker, Antje ;

Sougnez, Carrie ;

Onofrio, Robert ;

Ambrogio, Lauren ;

Auclair, Daniel ;

Fennell, Timothy ;

Carter, Scott L. ;

Drier, Yotam ;

Stojanov, Petar ;

Singer, Meredith A. ;

Voet, Douglas ;

Jing, Rui ;

Saksena, Gordon ;

Barretina, Jordi ;

Ramos, Alex H. ;

Pugh, Trevor J. ;

Stransky, Nicolas ;

Parkin, Melissa ;

Winckler, Wendy ;

Mahan, Scott ;

Ardlie, Kristin ;

Baldwin, Jennifer ;

Wargo, Jennifer ;

Schadendorf, Dirk ;

Meyerson, Matthew ;

Gabriel, Stacey B. ;

Golub, Todd R. ;

Wagner, Stephan N. ;

Lander, Eric S. ;

Getz, Gad ;

Chin, Lynda ;

Garraway, Levi A. .

NATURE, 2012, 485 (7399) :502-506

[7]

The genomic complexity of primary human prostate cancer [J].

Berger, Michael F. ;

Lawrence, Michael S. ;

Demichelis, Francesca ;

Drier, Yotam ;

Cibulskis, Kristian ;

Sivachenko, Andrey Y. ;

Sboner, Andrea ;

Esgueva, Raquel ;

Pflueger, Dorothee ;

Sougnez, Carrie ;

Onofrio, Robert ;

Carter, Scott L. ;

Park, Kyung ;

Habegger, Lukas ;

Ambrogio, Lauren ;

Fennell, Timothy ;

Parkin, Melissa ;

Saksena, Gordon ;

Voet, Douglas ;

Ramos, Alex H. ;

Pugh, Trevor J. ;

Wilkinson, Jane ;

Fisher, Sheila ;

Winckler, Wendy ;

Mahan, Scott ;

Ardlie, Kristin ;

Baldwin, Jennifer ;

Simons, Jonathan W. ;

Kitabayashi, Naoki ;

MacDonald, Theresa Y. ;

Kantoff, Philip W. ;

Chin, Lynda ;

Gabriel, Stacey B. ;

Gerstein, Mark B. ;

Golub, Todd R. ;

Meyerson, Matthew ;

Tewari, Ashutosh ;

Lander, Eric S. ;

Getz, Gad ;

Rubin, Mark A. ;

Garraway, Levi A. .

NATURE, 2011, 470 (7333) :214-220

[8]

Boland CR, 2010, GASTROENTEROLOGY, V138, P2073, DOI [10.1053/j.gastro.2009.12.064, 10.1053/j.gastro.2010.04.024]

[9]

APOBEC3B is an enzymatic source of mutation in breast cancer [J].

Burns, Michael B. ;

Lackey, Lela ;

Carpenter, Michael A. ;

Rathore, Anurag ;

Land, Allison M. ;

Leonard, Brandon ;

Refsland, Eric W. ;

Kotandeniya, Delshanee ;

Tretyakova, Natalia ;

Nikas, Jason B. ;

Yee, Douglas ;

Temiz, Nuri I. A. ;

Donohue, Duncan E. ;

McDougle, Rebecca M. ;

Brown, William L. ;

Law, Emily K. ;

Harris, Reuben S. .

NATURE, 2013, 494 (7437) :366-370

[10]

Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia [J].

De Keersmaecker, Kim ;

Atak, Zeynep Kalender ;

Li, Ning ;

Vicente, Carmen ;

Patchett, Stephanie ;

Girardi, Tiziana ;

Gianfelici, Valentina ;

Geerdens, Ellen ;

Clappier, Emmanuelle ;

Porcu, Michael ;

Lahortiga, Idoya ;

Luca, Rossella ;

Yan, Jiekun ;

Hulselmans, Gert ;

Vranckx, Hilde ;

Vandepoel, Roel ;

Sweron, Bram ;

Jacobs, Kris ;

Mentens, Nicole ;

Wlodarska, Iwona ;

Cauwelier, Barbara ;

Cloos, Jacqueline ;

Soulier, Jean ;

Uyttebroeck, Anne ;

Bagni, Claudia ;

Hassan, Bassem A. ;

Vandenberghe, Peter ;

Johnson, Arlen W. ;

Aerts, Stein ;

Cools, Jan .

NATURE GENETICS, 2013, 45 (02) :186-190

← 1 2 3 4 5 6 7 →