Patterns of somatic mutation in human cancer genomes

Christopher Greenman; Philip Stephens; Raffaella Smith; Gillian L Dalgliesh; Christopher Hunter; Graham Bignell; Helen Davies; Jon Teague; Adam Butler; Claire Stevens; Sarah Edkins; Sarah O'Meara; Imre Vastrik; Esther E Schmidt; Tim Avis; Syd Barthorpe; Gurpreet Bhamra; Gemma Buck; Bhudipa Choudhury; Jody Clements; Jennifer Cole; Ed Dicks; Simon Forbes; Kris Gray; Kelly Halliday; Rachel Harrison; Katy Hills; Jon Hinton; Andy Jenkinson; David Jones; Andy Menzies; Tatiana Mironenko; Janet Perry; Keiran Raine; Dave Richardson; Rebecca Shepherd; Alexandra Small; Calli Tofts; Jennifer Varian; Tony Webb; Sofie West; Sara Widaa; Andy Yates; Daniel P Cahill; David N Louis; Peter Goldstraw; Andrew G Nicholson; Francis Brasseur; Leendert Looijenga; Barbara L Weber; Yoke-Eng Chiew; Anna DeFazio; Mel F Greaves; Anthony R Green; Peter Campbell; Ewan Birney; Douglas F Easton; Georgia Chenevix-Trench; Min-Han Tan; Sok Kean Khoo; Bin Tean Teh; Siu Tsan Yuen; Suet Yi Leung; Richard Wooster; P Andrew Futreal; Michael R Stratton

doi:10.1038/nature05610

Patterns of somatic mutation in human cancer genomes

Christopher Greenman, Philip Stephens, Raffaella Smith, Gillian L Dalgliesh, Christopher Hunter, Graham Bignell, Helen Davies, Jon Teague, Adam Butler, Claire Stevens, Sarah Edkins, Sarah O'Meara, Imre Vastrik, Esther E Schmidt, Tim Avis, Syd Barthorpe, Gurpreet Bhamra, Gemma Buck, Bhudipa Choudhury, Jody ClementsJennifer Cole, Ed Dicks, Simon Forbes, Kris Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jon Hinton, Andy Jenkinson, David Jones, Andy Menzies, Tatiana Mironenko, Janet Perry, Keiran Raine, Dave Richardson, Rebecca Shepherd, Alexandra Small, Calli Tofts, Jennifer Varian, Tony Webb, Sofie West, Sara Widaa, Andy Yates, Daniel P Cahill, David N Louis, Peter Goldstraw, Andrew G Nicholson, Francis Brasseur, Leendert Looijenga, Barbara L Weber, Yoke-Eng Chiew, Anna DeFazio, Mel F Greaves, Anthony R Green, Peter Campbell, Ewan Birney, Douglas F Easton, Georgia Chenevix-Trench, Min-Han Tan, Sok Kean Khoo, Bin Tean Teh, Siu Tsan Yuen, Suet Yi Leung, Richard Wooster, P Andrew Futreal, Michael R Stratton

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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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.

Originele taal-2	Engels
Pagina's (van-tot)	153-8
Aantal pagina's	6
Tijdschrift	Nature
Volume	446
Nummer van het tijdschrift	7132
DOI's	https://doi.org/10.1038/nature05610
Status	Gepubliceerd - 8 mrt. 2007
Extern gepubliceerd	Ja

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10.1038/nature05610

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Greenman, C., Stephens, P., Smith, R., Dalgliesh, G. L., Hunter, C., Bignell, G., Davies, H., Teague, J., Butler, A., Stevens, C., Edkins, S., O'Meara, S., Vastrik, I., Schmidt, E. E., Avis, T., Barthorpe, S., Bhamra, G., Buck, G., Choudhury, B., ... Stratton, M. R. (2007). Patterns of somatic mutation in human cancer genomes. Nature, 446(7132), 153-8. https://doi.org/10.1038/nature05610

@article{7948368ed073494cae50b643c7688edf,

title = "Patterns of somatic mutation in human cancer genomes",

abstract = "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.",

keywords = "Amino Acid Sequence, DNA Mutational Analysis, Genes, Neoplasm/genetics, Genome, Human/genetics, Genomics, Humans, Molecular Sequence Data, Mutation/genetics, Neoplasm Proteins/chemistry, Neoplasms/genetics, Protein Kinases/chemistry",

author = "Christopher Greenman and Philip Stephens and Raffaella Smith and Dalgliesh, {Gillian L} and Christopher Hunter and Graham Bignell and Helen Davies and Jon Teague and Adam Butler and Claire Stevens and Sarah Edkins and Sarah O'Meara and Imre Vastrik and Schmidt, {Esther E} and Tim Avis and Syd Barthorpe and Gurpreet Bhamra and Gemma Buck and Bhudipa Choudhury and Jody Clements and Jennifer Cole and Ed Dicks and Simon Forbes and Kris Gray and Kelly Halliday and Rachel Harrison and Katy Hills and Jon Hinton and Andy Jenkinson and David Jones and Andy Menzies and Tatiana Mironenko and Janet Perry and Keiran Raine and Dave Richardson and Rebecca Shepherd and Alexandra Small and Calli Tofts and Jennifer Varian and Tony Webb and Sofie West and Sara Widaa and Andy Yates and Cahill, {Daniel P} and Louis, {David N} and Peter Goldstraw and Nicholson, {Andrew G} and Francis Brasseur and Leendert Looijenga and Weber, {Barbara L} and Yoke-Eng Chiew and Anna DeFazio and Greaves, {Mel F} and Green, {Anthony R} and Peter Campbell and Ewan Birney and Easton, {Douglas F} and Georgia Chenevix-Trench and Min-Han Tan and Khoo, {Sok Kean} and Teh, {Bin Tean} and Yuen, {Siu Tsan} and Leung, {Suet Yi} and Richard Wooster and Futreal, {P Andrew} and Stratton, {Michael R}",

note = "Funding Information: Acknowledgements We would like to thank J. Leary and the ABN-Oncology group (funded by the National Health and Medical Research Council of Australia), the Hauenstein Foundation and the Cooperative Human Tissue Network for providing samples for analysis, G. Wu and L. Stein for the development of the joint Reactome, Panther, INOH database, and C. Marshall and N. Rahman for comments. The studies were funded by the NIH and the Wellcome Trust.",

year = "2007",

month = mar,

day = "8",

doi = "10.1038/nature05610",

language = "English",

volume = "446",

pages = "153--8",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7132",

}

Greenman, C, Stephens, P, Smith, R, Dalgliesh, GL, Hunter, C, Bignell, G, Davies, H, Teague, J, Butler, A, Stevens, C, Edkins, S, O'Meara, S, Vastrik, I, Schmidt, EE, Avis, T, Barthorpe, S, Bhamra, G, Buck, G, Choudhury, B, Clements, J, Cole, J, Dicks, E, Forbes, S, Gray, K, Halliday, K, Harrison, R, Hills, K, Hinton, J, Jenkinson, A, Jones, D, Menzies, A, Mironenko, T, Perry, J, Raine, K, Richardson, D, Shepherd, R, Small, A, Tofts, C, Varian, J, Webb, T, West, S, Widaa, S, Yates, A, Cahill, DP, Louis, DN, Goldstraw, P, Nicholson, AG, Brasseur, F, Looijenga, L, Weber, BL, Chiew, Y-E, DeFazio, A, Greaves, MF, Green, AR, Campbell, P, Birney, E, Easton, DF, Chenevix-Trench, G, Tan, M-H, Khoo, SK, Teh, BT, Yuen, ST, Leung, SY, Wooster, R, Futreal, PA & Stratton, MR 2007, 'Patterns of somatic mutation in human cancer genomes', Nature, vol. 446, nr. 7132, blz. 153-8. https://doi.org/10.1038/nature05610

TY - JOUR

T1 - Patterns of somatic mutation in human cancer genomes

AU - Greenman, Christopher

AU - Stephens, Philip

AU - Smith, Raffaella

AU - Dalgliesh, Gillian L

AU - Hunter, Christopher

AU - Bignell, Graham

AU - Davies, Helen

AU - Teague, Jon

AU - Butler, Adam

AU - Stevens, Claire

AU - Edkins, Sarah

AU - O'Meara, Sarah

AU - Vastrik, Imre

AU - Schmidt, Esther E

AU - Avis, Tim

AU - Barthorpe, Syd

AU - Bhamra, Gurpreet

AU - Buck, Gemma

AU - Choudhury, Bhudipa

AU - Clements, Jody

AU - Cole, Jennifer

AU - Dicks, Ed

AU - Forbes, Simon

AU - Gray, Kris

AU - Halliday, Kelly

AU - Harrison, Rachel

AU - Hills, Katy

AU - Hinton, Jon

AU - Jenkinson, Andy

AU - Jones, David

AU - Menzies, Andy

AU - Mironenko, Tatiana

AU - Perry, Janet

AU - Raine, Keiran

AU - Richardson, Dave

AU - Shepherd, Rebecca

AU - Small, Alexandra

AU - Tofts, Calli

AU - Varian, Jennifer

AU - Webb, Tony

AU - West, Sofie

AU - Widaa, Sara

AU - Yates, Andy

AU - Cahill, Daniel P

AU - Louis, David N

AU - Goldstraw, Peter

AU - Nicholson, Andrew G

AU - Brasseur, Francis

AU - Looijenga, Leendert

AU - Weber, Barbara L

AU - Chiew, Yoke-Eng

AU - DeFazio, Anna

AU - Greaves, Mel F

AU - Green, Anthony R

AU - Campbell, Peter

AU - Birney, Ewan

AU - Easton, Douglas F

AU - Chenevix-Trench, Georgia

AU - Tan, Min-Han

AU - Khoo, Sok Kean

AU - Teh, Bin Tean

AU - Yuen, Siu Tsan

AU - Leung, Suet Yi

AU - Wooster, Richard

AU - Futreal, P Andrew

AU - Stratton, Michael R

N1 - Funding Information: Acknowledgements We would like to thank J. Leary and the ABN-Oncology group (funded by the National Health and Medical Research Council of Australia), the Hauenstein Foundation and the Cooperative Human Tissue Network for providing samples for analysis, G. Wu and L. Stein for the development of the joint Reactome, Panther, INOH database, and C. Marshall and N. Rahman for comments. The studies were funded by the NIH and the Wellcome Trust.

PY - 2007/3/8

Y1 - 2007/3/8

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - DNA Mutational Analysis

KW - Genes, Neoplasm/genetics

KW - Genome, Human/genetics

KW - Genomics

KW - Humans

KW - Molecular Sequence Data

KW - Mutation/genetics

KW - Neoplasm Proteins/chemistry

KW - Neoplasms/genetics

KW - Protein Kinases/chemistry

UR - http://www.scopus.com/inward/record.url?scp=33947101019&partnerID=8YFLogxK

U2 - 10.1038/nature05610

DO - 10.1038/nature05610

M3 - Article

C2 - 17344846

SN - 0028-0836

VL - 446

SP - 153

EP - 158

JO - Nature

JF - Nature

IS - 7132

ER -

Patterns of somatic mutation in human cancer genomes

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