Patterns of somatic mutation in human cancer genomes

被引：2308

作者：

Greenman, Christopher

Stephens, Philip

Smith, Raffaella

Dalgliesh, Gillian L.

Hunter, Christopher

Bignell, Graham

Davies, Helen

Teague, Jon

Butler, Adam

Edkins, Sarah

O'Meara, Sarah

Vastrik, Imre

Schmidt, Esther E.

Avis, Tim

Barthorpe, Syd

Bhamra, Gurpreet

Buck, Gemma

Choudhury, Bhudipa

Clements, Jody

Cole, Jennifer

Dicks, Ed

Forbes, Simon

Gray, Kris

Halliday, Kelly

Harrison, Rachel

Hills, Katy

Hinton, Jon

Jenkinson, Andy

Jones, David

Menzies, Andy

Mironenko, Tatiana

Perry, Janet

Raine, Keiran

Richardson, Dave

Shepherd, Rebecca

Small, Alexandra

Tofts, Calli

Varian, Jennifer

Webb, Tony

West, Sofie

Widaa, Sara

Yates, Andy

Cahill, Daniel P.

Louis, David N.

Goldstraw, Peter

Nicholson, Andrew G.

Brasseur, Francis

Looijenga, Leendert

Weber, Barbara L.

Chiew, Yoke-Eng

机构：

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

[2] EMBL, European Bioinformat Inst, Cambridge CB10 1SD, England

[3] Massachusetts Gen Hosp, Neurosurg Serv, Mol Pathol Unit, Boston, MA 02114 USA

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

[5] Harvard Univ, Sch Med, Boston, MA 02114 USA

[6] Royal Brompton Hosp, London SW3 6NP, England

[7] Ludwig Inst Canc Res, B-1200 Brussels, Belgium

[8] Erasmus MC, Daniel den Hoed Canc Ctr, Josephine Nefkens Inst, Lab Pathol Expt Pathooncol, NL-3000 DR Rotterdam, Netherlands

[9] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA

[10] Westmead Hosp, Dept Gynaecol Oncol, Westmead, NSW 2145, Australia

[11] Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Westmead, NSW 2145, Australia

[12] Inst Canc Res, Sutton SM2 5NG, Surrey, England

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

[14] Univ Cambridge, Cambridge CB2 0QQ, England

[15] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 8RN, England

[16] Univ Queensland, Royal Brisbane Hosp, Queensland Inst Med Res, Herston, Qld 4029, Australia

[17] Van Andel Res Inst, Grand Rapids, MI 49503 USA

[18] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China

来源：

NATURE | 2007年 / 446卷 / 7132期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1038/nature05610

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：

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.

引用

页码：153 / 158

页数：6

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