Discovery and saturation analysis of cancer genes across 21 tumour types

被引：2328

作者：

Lawrence, Michael S. ^{[1
]}

Stojanov, Petar ^{[1
,2
]}

Mermel, Craig H. ^{[1
,3
,4
]}

Robinson, James T. ^{[1
]}

Garraway, Levi A. ^{[1
,2
,5
]}

Golub, Todd R. ^{[1
,2
,5
,6
]}

Meyerson, Matthew ^{[1
,2
,5
]}

Gabriel, Stacey B. ^{[1
]}

Lander, Eric S. ^{[1
,5
,7
]}

Getz, Gad ^{[1
,3
,4
,5
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA

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

[3] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

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

[6] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[7] MIT, Cambridge, MA 02139 USA

来源：

NATURE | 2014年 / 505卷 / 7484期

关键词：

MUTATIONS;

D O I：

10.1038/nature12912

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：

07 ; 0710 ; 09 ;

摘要：

Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 6005,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics.

引用

页码：495 / +

页数：9

共 13 条

[1] Absolute quantification of somatic DNA alterations in human cancer [J].

Carter, Scott L. ;

Cibulskis, Kristian ;

Helman, Elena ;

McKenna, Aaron ;

Shen, Hui ;

Zack, Travis ;

Laird, Peter W. ;

Onofrio, Robert C. ;

Winckler, Wendy ;

Weir, Barbara A. ;

Beroukhim, Rameen ;

Pellman, David ;

Levine, Douglas A. ;

Lander, Eric S. ;

Meyerson, Matthew ;

Getz, Gad .

NATURE BIOTECHNOLOGY, 2012, 30 (05) :413-+

[2] Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples [J].

Cibulskis, Kristian ;

Lawrence, Michael S. ;

Carter, Scott L. ;

Sivachenko, Andrey ;

Jaffe, David ;

Sougnez, Carrie ;

Gabriel, Stacey ;

Meyerson, Matthew ;

Lander, Eric S. ;

Getz, Gad .

NATURE BIOTECHNOLOGY, 2013, 31 (03) :213-219

[3] Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].

Ferlay, Jacques ;

Shin, Hai-Rim ;

Bray, Freddie ;

Forman, David ;

Mathers, Colin ;

Parkin, Donald Maxwell .

INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917

[4] Lessons from the Cancer Genome [J].

Garraway, Levi A. ;

Lander, Eric S. .

CELL, 2013, 153 (01) :17-37

[5] Integrated genomic characterization of endometrial carcinoma [J].

Getz, Gad ;

Gabriel, Stacey B. ;

Cibulskis, Kristian ;

Lander, Eric ;

Sivachenko, Andrey ;

Sougnez, Carrie ;

Lawrence, Mike ;

Kandoth, Cyriac ;

Dooling, David ;

Fulton, Robert ;

Fulton, Lucinda ;

Kalicki-Veizer, Joelle ;

McLellan, Michael D. ;

O'Laughlin, Michelle ;

Schmidt, Heather ;

Wilson, Richard K. ;

Ye, Kai ;

Ding, Li ;

Mardis, Elaine R. ;

Ally, Adrian ;

Balasundaram, Miruna ;

Birol, Inanc ;

Butterfield, Yaron S. N. ;

Carlsen, Rebecca ;

Carter, Candace ;

Chu, Andy ;

Chuah, Eric ;

Chun, Hye-Jung E. ;

Dhalla, Noreen ;

Guin, Ranabir ;

Hirst, Carrie ;

Holt, Robert A. ;

Jones, Steven J. M. ;

Lee, Darlene ;

Li, Haiyan I. ;

Marra, Marco A. ;

Mayo, Michael ;

Moore, Richard A. ;

Mungall, Andrew J. ;

Plettner, Patrick ;

Schein, Jacqueline E. ;

Sipahimalani, Payal ;

Tam, Angela ;

Varhol, Richard J. ;

Robertson, A. Gordon ;

Pashtan, Itai ;

Saksena, Gordon ;

Onofrio, Robert C. ;

Schumacher, Steven E. ;

Tabak, Barbara .

NATURE, 2013, 497 (7447) :67-73

[6] Hallmarks of Cancer: The Next Generation [J].

Hanahan, Douglas ;

Weinberg, Robert A. .

CELL, 2011, 144 (05) :646-674

[7] Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing [J].

Imielinski, Marcin ;

Berger, Alice H. ;

Hammerman, Peter S. ;

Hernandez, Bryan ;

Pugh, Trevor J. ;

Hodis, Eran ;

Cho, Jeonghee ;

Suh, James ;

Capelletti, Marzia ;

Sivachenko, Andrey ;

Sougnez, Carrie ;

Auclair, Daniel ;

Lawrence, Michael S. ;

Stojanov, Petar ;

Cibulskis, Kristian ;

Choi, Kyusam ;

de Waal, Luc ;

Sharifnia, Tanaz ;

Brooks, Angela ;

Greulich, Heidi ;

Banerji, Shantanu ;

Zander, Thomas ;

Seidel, Danila ;

Leenders, Frauke ;

Ansen, Sascha ;

Ludwig, Corinna ;

Engel-Riedel, Walburga ;

Stoelben, Erich ;

Wolf, Juergen ;

Goparju, Chandra ;

Thompson, Kristin ;

Winckler, Wendy ;

Kwiatkowski, David ;

Johnson, Bruce E. ;

Jaenne, Pasi A. ;

Miller, Vincent A. ;

Pao, William ;

Travis, William D. ;

Pass, Harvey I. ;

Gabriel, Stacey B. ;

Lander, Eric S. ;

Thomas, Roman K. ;

Garraway, Levi A. ;

Getz, Gad ;

Meyerson, Matthew .

CELL, 2012, 150 (06) :1107-1120

[8] Mutational landscape and significance across 12 major cancer types [J].

Kandoth, Cyriac ;

McLellan, Michael D. ;

Vandin, Fabio ;

Ye, Kai ;

Niu, Beifang ;

Lu, Charles ;

Xie, Mingchao ;

Zhang, Qunyuan ;

McMichael, Joshua F. ;

Wyczalkowski, Matthew A. ;

Leiserson, Mark D. M. ;

Miller, Christopher A. ;

Welch, John S. ;

Walter, Matthew J. ;

Wendl, Michael C. ;

Ley, Timothy J. ;

Wilson, Richard K. ;

Raphael, Benjamin J. ;

Ding, Li .

NATURE, 2013, 502 (7471) :333-+

[9] Mutational heterogeneity in cancer and the search for new cancer-associated genes [J].

Lawrence, Michael S. ;

Stojanov, Petar ;

Polak, Paz ;

Kryukov, Gregory V. ;

Cibulskis, Kristian ;

Sivachenko, Andrey ;

Carter, Scott L. ;

Stewart, Chip ;

Mermel, Craig H. ;

Roberts, Steven A. ;

Kiezun, Adam ;

Hammerman, Peter S. ;

McKenna, Aaron ;

Drier, Yotam ;

Zou, Lihua ;

Ramos, Alex H. ;

Pugh, Trevor J. ;

Stransky, Nicolas ;

Helman, Elena ;

Kim, Jaegil ;

Sougnez, Carrie ;

Ambrogio, Lauren ;

Nickerson, Elizabeth ;

Shefler, Erica ;

Cortes, Maria L. ;

Auclair, Daniel ;

Saksena, Gordon ;

Voet, Douglas ;

Noble, Michael ;

DiCara, Daniel ;

Lin, Pei ;

Lichtenstein, Lee ;

Heiman, David I. ;

Fennell, Timothy ;

Imielinski, Marcin ;

Hernandez, Bryan ;

Hodis, Eran ;

Baca, Sylvan ;

Dulak, Austin M. ;

Lohr, Jens ;

Landau, Dan-Avi ;

Wu, Catherine J. ;

Melendez-Zajgla, Jorge ;

Hidalgo-Miranda, Alfredo ;

Koren, Amnon ;

McCarroll, Steven A. ;

Mora, Jaume ;

Lee, Ryan S. ;

Crompton, Brian ;

Onofrio, Robert .

NATURE, 2013, 499 (7457) :214-218

[10] Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing [J].

Lohr, Jens G. ;

Stojanov, Petar ;

Lawrence, Michael S. ;

Auclair, Daniel ;

Chapuy, Bjoern ;

Sougnez, Carrie ;

Cruz-Gordillo, Peter ;

Knoechel, Birgit ;

Asmann, Yan W. ;

Slager, Susan L. ;

Novak, Anne J. ;

Dogan, Ahmet ;

Ansell, Stephen M. ;

Link, Brian K. ;

Zou, Lihua ;

Gould, Joshua ;

Saksena, Gordon ;

Stransky, Nicolas ;

Rangel-Escareno, Claudia ;

Carlos Fernandez-Lopez, Juan ;

Hidalgo-Miranda, Alfredo ;

Melendez-Zajgla, Jorge ;

Hernandez-Lemus, Enrique ;

Schwarz-Cruz y Celis, Angela ;

Imaz-Rosshandler, Ivan ;

Ojesina, Akinyemi I. ;

Jung, Joonil ;

Pedamallu, Chandra S. ;

Lander, Eric S. ;

Habermann, Thomas M. ;

Cerhan, James R. ;

Shipp, Margaret A. ;

Getz, Gad ;

Golub, Todd R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (10) :3879-3884

← 1 2 →