Patterns of somatic mutation in human cancer genomes.

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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 YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR

Patterns of somatic mutation in human cancer genomes.

Nature. 2007 Mar 8;446(7132):153-8.

PubMed ID
17344846 [ View in PubMed
]
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.

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Polypeptides
NameUniProt ID
Tyrosine-protein kinase ABL1P00519Details
G protein-coupled receptor kinase 3P35626Details
Vascular endothelial growth factor receptor 3P35916Details
Vascular endothelial growth factor receptor 1P17948Details
Insulin receptorP06213Details
RAF proto-oncogene serine/threonine-protein kinaseP04049Details
Receptor-type tyrosine-protein kinase FLT3P36888Details
Platelet-derived growth factor receptor betaP09619Details
Activin receptor type-1Q04771Details
Beta-adrenergic receptor kinase 1P25098Details
ALK tyrosine kinase receptorQ9UM73Details
Vascular endothelial growth factor receptor 2P35968Details
Serine/threonine-protein kinase A-RafP10398Details
Tyrosine-protein kinase ABL2P42684Details
Cyclin-dependent kinase 15Q96Q40Details
Mast/stem cell growth factor receptor KitP10721Details
Receptor tyrosine-protein kinase erbB-2P04626Details
Atrial natriuretic peptide receptor 1P16066Details
Serine/threonine-protein kinase B-rafP15056Details
Activin receptor type-1BP36896Details
Fibroblast growth factor receptor 2P21802Details
Epidermal growth factor receptorP00533Details
Activated CDC42 kinase 1Q07912Details
Proto-oncogene tyrosine-protein kinase SrcP12931Details
Tyrosine-protein kinase FynP06241Details
Tyrosine-protein kinase YesP07947Details
Ephrin type-A receptor 2P29317Details
Platelet-derived growth factor receptor alphaP16234Details
Macrophage colony-stimulating factor 1 receptorP07333Details
Insulin-like growth factor 1 receptorP08069Details
Protein-tyrosine kinase 2-betaQ14289Details
Protein kinase C beta typeP05771Details
Cyclin-dependent kinase 5Q00535Details
Hepatocyte growth factor receptorP08581Details
Aurora kinase AO14965Details
Atrial natriuretic peptide receptor 2P20594Details
Rho-associated protein kinase 1Q13464Details
Mitogen-activated protein kinase 14Q16539Details
High affinity nerve growth factor receptorP04629Details
Mitogen-activated protein kinase 3P27361Details
Cyclin-dependent kinase 2P24941Details
Epithelial discoidin domain-containing receptor 1Q08345Details
Protein kinase C alpha typeP17252Details
Inhibitor of nuclear factor kappa-B kinase subunit betaO14920Details
RAC-beta serine/threonine-protein kinaseP31751Details
Fibroblast growth factor receptor 4P22455Details
Serine/threonine-protein kinase pim-1P11309Details
Tyrosine-protein kinase BTKQ06187Details
Tyrosine-protein kinase ZAP-70P43403Details
Tyrosine-protein kinase ITK/TSKQ08881Details
Tyrosine-protein kinase CSKP41240Details
MAP kinase-activated protein kinase 2P49137Details
Protein kinase C theta typeQ04759Details
Tyrosine-protein kinase HCKP08631Details
Death-associated protein kinase 1P53355Details
Dual specificity protein kinase CLK1P49759Details
TGF-beta receptor type-2P37173Details
Cyclin-dependent kinase 7P50613Details
Fibroblast growth factor receptor 1P11362Details
Fibroblast growth factor receptor 3P22607Details
Cyclin-dependent kinase 9P50750Details
Cyclin-dependent kinase 6Q00534Details
Cyclin-dependent kinase 4P11802Details
Cyclin-dependent kinase 8P49336Details
DNA-dependent protein kinase catalytic subunitP78527Details
Serine/threonine-protein kinase mTORP42345Details
Tyrosine-protein kinase JAK2O60674Details
Proto-oncogene tyrosine-protein kinase receptor RetP07949Details
Ephrin type-B receptor 4P54760Details
N-terminal kinase-like proteinQ96KG9Details
Peripheral plasma membrane protein CASKO14936Details
Mitogen-activated protein kinase 12P53778Details
Focal adhesion kinase 1Q05397Details
Casein kinase I isoform gamma-2P78368Details
Wee1-like protein kinaseP30291Details
Angiopoietin-1 receptorQ02763Details
Serine/threonine-protein kinase Chk1O14757Details
Mitogen-activated protein kinase 11Q15759Details
Mitogen-activated protein kinase 13O15264Details
Aurora kinase BQ96GD4Details
Mitogen-activated protein kinase kinase kinase 1Q13233Details
Protein kinase C epsilon typeQ02156Details
Activin receptor type-2AP27037Details
Tyrosine-protein kinase JAK3P52333Details
Guanylyl cyclase CP25092Details
Casein kinase I isoform epsilonP49674Details
BDNF/NT-3 growth factors receptorQ16620Details
Serine/threonine-protein kinase PLK1P53350Details
cAMP-dependent protein kinase catalytic subunit alphaP17612Details
Mitogen-activated protein kinase 9P45984Details
TGF-beta receptor type-1P36897Details
Death-associated protein kinase 3O43293Details
Mitogen-activated protein kinase 8P45983Details
Calcium/calmodulin-dependent protein kinase type II subunit betaQ13554Details
Serine/threonine-protein kinase haspinQ8TF76Details
Serine/threonine-protein kinase Nek2P51955Details
Serine/threonine-protein kinase/endoribonuclease IRE1O75460Details
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrialQ15118Details
Protein kinase C iota typeP41743Details
Myotonin-protein kinaseQ09013Details
Casein kinase II subunit alpha'P19784Details
Dual specificity tyrosine-phosphorylation-regulated kinase 1AQ13627Details
STE20-like serine/threonine-protein kinaseQ9H2G2Details
Calcium/calmodulin-dependent protein kinase type IVQ16566Details
Dual specificity protein kinase CLK3P49761Details
MAP kinase-activated protein kinase 3Q16644Details
Serine/threonine-protein kinase Sgk1O00141Details
Calcium/calmodulin-dependent protein kinase type II subunit deltaQ13557Details
Serine/threonine-protein kinase 26Q9P289Details
Ephrin type-A receptor 7Q15375Details
Tyrosine-protein kinase JAK1P23458Details
Non-receptor tyrosine-protein kinase TYK2P29597Details
Calcium/calmodulin-dependent protein kinase type 1GQ96NX5Details
Rho-associated protein kinase 2O75116Details
Casein kinase I isoform gamma-1Q9HCP0Details
Tyrosine-protein kinase MerQ12866Details
Ribosomal protein S6 kinase alpha-1Q15418Details
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrialQ16654Details
Tyrosine-protein kinase LynP07948Details
SRSF protein kinase 2P78362Details
Calcium/calmodulin-dependent protein kinase type 1DQ8IU85Details
Serine/threonine-protein kinase 17BO94768Details
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrialQ15120Details
Interleukin-1 receptor-associated kinase 4Q9NWZ3Details
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrialQ15119Details
Mitogen-activated protein kinase kinase kinase 9P80192Details
cAMP-dependent protein kinase catalytic subunit betaP22694Details
Ephrin type-B receptor 2P29323Details
Aurora kinase CQ9UQB9Details
Ribosomal protein S6 kinase alpha-4O75676Details
Transient receptor potential cation channel subfamily M member 7Q96QT4Details
Inhibitor of nuclear factor kappa-B kinase subunit alphaO15111Details
Protein-tyrosine kinase 6Q13882Details
Discoidin domain-containing receptor 2Q16832Details
Tyrosine-protein kinase FRKP42685Details
Breakpoint cluster region proteinP11274Details
Mitogen-activated protein kinase kinase kinase 2Q9Y2U5Details
Serine/threonine-protein kinase SIK1P57059Details
Serine/threonine-protein kinase Nek11Q8NG66Details
LIM domain kinase 1P53667Details
Receptor tyrosine-protein kinase erbB-4Q15303Details
Serine-protein kinase ATMQ13315Details
Ribosomal protein S6 kinase alpha-3P51812Details
Protein kinase C zeta typeQ05513Details
5'-AMP-activated protein kinase catalytic subunit alpha-2P54646Details
Myosin light chain kinase 2, skeletal/cardiac muscleQ9H1R3Details
Transient receptor potential cation channel subfamily M member 6Q9BX84Details
Tyrosine-protein kinase FgrP09769Details
Ephrin type-A receptor 5P54756Details
Mitogen-activated protein kinase kinase kinase 20Q9NYL2Details
Bone morphogenetic protein receptor type-1AP36894Details
Bone morphogenetic protein receptor type-2Q13873Details
Ribosomal protein S6 kinase alpha-6Q9UK32Details
Atypical kinase COQ8A, mitochondrialQ8NI60Details
Serine/threonine-protein kinase NIM1Q8IY84Details
Serine/threonine-protein kinase 24Q9Y6E0Details
Serine/threonine-protein kinase 3Q13188Details
Tyrosine-protein kinase TecP42680Details
Serine/threonine-protein kinase 33Q9BYT3Details
Serine/threonine-protein kinase 36Q9NRP7Details
Serine/threonine-protein kinase 38Q15208Details
Serine/threonine-protein kinase 38-likeQ9Y2H1Details
Serine/threonine-protein kinase TAO1Q7L7X3Details
Serine/threonine-protein kinase TAO3Q9H2K8Details
Serine/threonine-protein kinase TBK1Q9UHD2Details
Dual specificity testis-specific protein kinase 1Q15569Details
Tyrosine-protein kinase receptor Tie-1P35590Details
Serine/threonine-protein kinase tousled-like 1Q9UKI8Details
Serine/threonine-protein kinase tousled-like 2Q86UE8Details
TRAF2 and NCK-interacting protein kinaseQ9UKE5Details
Non-receptor tyrosine-protein kinase TNK1Q13470Details
Serine/threonine-protein kinase TNNI3KQ59H18Details
Testis-specific serine/threonine-protein kinase 1Q9BXA7Details
Tyrosine-protein kinase TXKP42681Details
Tyrosine-protein kinase receptor TYRO3Q06418Details
Serine/threonine-protein kinase ULK1O75385Details
Serine/threonine-protein kinase ULK2Q8IYT8Details
Mitogen-activated protein kinase kinase kinase 19Q56UN5Details
AP2-associated protein kinase 1Q2M2I8Details
Atypical kinase COQ8B, mitochondrialQ96D53Details
Ankyrin repeat and protein kinase domain-containing protein 1Q8NFD2Details
Tyrosine-protein kinase receptor UFOP30530Details
Tyrosine-protein kinase BlkP51451Details
BMP-2-inducible protein kinaseQ9NSY1Details
Bone morphogenetic protein receptor type-1BO00238Details
Cytoplasmic tyrosine-protein kinase BMXP51813Details
Calcium/calmodulin-dependent protein kinase type 1Q14012Details
Calcium/calmodulin-dependent protein kinase kinase 1Q8N5S9Details
Calcium/calmodulin-dependent protein kinase kinase 2Q96RR4Details
Serine/threonine-protein kinase MRCK gammaQ6DT37Details
Cyclin-dependent kinase-like 1Q00532Details
Cyclin-dependent kinase-like 2Q92772Details
Citron Rho-interacting kinaseO14578Details
Dual specificity protein kinase CLK4Q9HAZ1Details
Casein kinase I isoform alphaP48729Details
Death-associated protein kinase 2Q9UIK4Details
Serine/threonine-protein kinase DCLK1O15075Details
Serine/threonine-protein kinase DCLK2Q8N568Details
Serine/threonine-protein kinase DCLK3Q9C098Details
Dual specificity tyrosine-phosphorylation-regulated kinase 1BQ9Y463Details
Eukaryotic translation initiation factor 2-alpha kinase 1Q9BQI3Details
Interferon-induced, double-stranded RNA-activated protein kinaseP19525Details
eIF-2-alpha kinase GCN2Q9P2K8Details
Ephrin type-A receptor 1P21709Details
Ephrin type-A receptor 3P29320Details
Ephrin type-A receptor 4P54764Details
Ephrin type-A receptor 6Q9UF33Details
Ephrin type-A receptor 8P29322Details
Ephrin type-B receptor 1P54762Details
Ephrin type-B receptor 6O15197Details
Tyrosine-protein kinase FerP16591Details
Tyrosine-protein kinase Fes/FpsP07332Details
Cyclin-G-associated kinaseO14976Details
Glycogen synthase kinase-3 alphaP49840Details
Homeodomain-interacting protein kinase 2Q9H2X6Details
Homeodomain-interacting protein kinase 3Q9H422Details
Serine/threonine-protein kinase ICKQ9UPZ9Details
Inhibitor of nuclear factor kappa-B kinase subunit epsilonQ14164Details
Insulin receptor-related proteinP14616Details
Interleukin-1 receptor-associated kinase 1P51617Details
Interleukin-1 receptor-associated kinase 3Q9Y616Details
Serine/threonine-protein kinase LATS1O95835Details
LIM domain kinase 2P53671Details
Leucine-rich repeat serine/threonine-protein kinase 2Q5S007Details
Leukocyte tyrosine kinase receptorP29376Details
Dual specificity mitogen-activated protein kinase kinase 3P46734Details
Dual specificity mitogen-activated protein kinase kinase 5Q13163Details
Mitogen-activated protein kinase kinase kinase 10Q02779Details
Mitogen-activated protein kinase kinase kinase 11Q16584Details
Mitogen-activated protein kinase kinase kinase 12Q12852Details
Mitogen-activated protein kinase kinase kinase 13O43283Details
Mitogen-activated protein kinase kinase kinase 15Q6ZN16Details
Mitogen-activated protein kinase kinase kinase 3Q99759Details
Mitogen-activated protein kinase kinase kinase 4Q9Y6R4Details
Mitogen-activated protein kinase kinase kinase 6O95382Details
Mitogen-activated protein kinase kinase kinase kinase 1Q92918Details
Mitogen-activated protein kinase kinase kinase kinase 3Q8IVH8Details
Mitogen-activated protein kinase kinase kinase kinase 4O95819Details
Mitogen-activated protein kinase kinase kinase kinase 5Q9Y4K4Details
Mitogen-activated protein kinase 4P31152Details
Mitogen-activated protein kinase 7Q13164Details
MAP kinase-activated protein kinase 5Q8IW41Details
Serine/threonine-protein kinase MARK1Q9P0L2Details
MAP/microtubule affinity-regulating kinase 3P27448Details
MAP/microtubule affinity-regulating kinase 4Q96L34Details
Microtubule-associated serine/threonine-protein kinase 1Q9Y2H9Details
Megakaryocyte-associated tyrosine-protein kinaseP42679Details
Maternal embryonic leucine zipper kinaseQ14680Details
Misshapen-like kinase 1Q8N4C8Details
MAP kinase-interacting serine/threonine-protein kinase 1Q9BUB5Details
MAP kinase-interacting serine/threonine-protein kinase 2Q9HBH9Details
Macrophage-stimulating protein receptorQ04912Details
Muscle, skeletal receptor tyrosine-protein kinaseO15146Details
Myosin light chain kinase, smooth muscleQ15746Details
Myosin light chain kinase family member 4Q86YV6Details
Myosin-IIIaQ8NEV4Details
Serine/threonine-protein kinase Nek1Q96PY6Details
Serine/threonine-protein kinase Nek3P51956Details
Serine/threonine-protein kinase Nek4P51957Details
Serine/threonine-protein kinase Nek5Q6P3R8Details
Serine/threonine-protein kinase Nek9Q8TD19Details
NT-3 growth factor receptorQ16288Details
NUAK family SNF1-like kinase 1O60285Details
NUAK family SNF1-like kinase 2Q9H093Details
Serine/threonine-protein kinase OSR1O95747Details
Serine/threonine-protein kinase PAK 3O75914Details
Serine/threonine-protein kinase PAK 4O96013Details
Serine/threonine-protein kinase PAK 6Q9NQU5Details
Serine/threonine-protein kinase PAK 5Q9P286Details
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoformQ16816Details
Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinaseQ99640Details
Serine/threonine-protein kinase N1Q16512Details
Serine/threonine-protein kinase PLK2Q9NYY3Details
Serine/threonine-protein kinase PLK4O00444Details
Serine/threonine-protein kinase D1Q15139Details
cGMP-dependent protein kinase 2Q13237Details
Serine/threonine-protein kinase PRP4 homologQ13523Details
Serine/threonine-protein kinase RIO2Q9BVS4Details
Serine/threonine-protein kinase RIO3O14730Details
Receptor-interacting serine/threonine-protein kinase 1Q13546Details
Receptor-interacting serine/threonine-protein kinase 2O43353Details
Receptor-interacting serine/threonine-protein kinase 4P57078Details
Proto-oncogene tyrosine-protein kinase ROSP08922Details
Serine/threonine-protein kinase SBK1Q52WX2Details
Serine/threonine-protein kinase Sgk3Q96BR1Details
Serine/threonine-protein kinase SIK2Q9H0K1Details
SNF-related serine/threonine-protein kinaseQ9NRH2Details
Tyrosine-protein kinase SrmsQ9H3Y6Details
Serine/threonine-protein kinase 10O94804Details
Serine/threonine-protein kinase 16O75716Details
Serine/threonine-protein kinase 17AQ9UEE5Details
Serine/threonine-protein kinase 32AQ8WU08Details
Mitogen-activated protein kinase 6Q16659Details
Receptor tyrosine-protein kinase erbB-3P21860Details
Serine/threonine-protein kinase ATRQ13535Details
Dual specificity mitogen-activated protein kinase kinase 4P45985Details
Dual specificity mitogen-activated protein kinase kinase 7O14733Details
cAMP-dependent protein kinase catalytic subunit gammaP22612Details