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1、UKPMCFundersGroupAuthorManuscriptNatRevCancer.Authormanuscript;availableinPMC2009April5.Publishedinfinaleditedformas:NatRevCancer.2004March;4(3):177±183.doi:10.1038/nrc1299.UKPMCFundersGroupAuthorManuscriptUKPMCFundersGroupAuthorManuscriptACENSUSOFHUMANCANC
2、ERGENESP.AndrewFutreal*,LachlanCoin*,MhairiMarshall*,ThomasDown*,TimothyHubbard*,RichardWooster*,NazneenRahman‡,andMichaelR.Stratton*,‡*CancerGenomeProject,HumanGenomeAnalysisGroupandPfamGroup,WellcomeTrustSangerInstitute,WellcomeTrustGenomeCampus,HinxtonCa
3、mbs,CB101SA,UK.‡SectionofCancerGenetics,InstituteofCancerResearch,15CotswoldRd,Sutton,SurreySM25NG,UK.AbstractAcentralaimofcancerresearchhasbeentoidentifythemutatedgenesthatarecausallyimplicatedinoncogenesis(‘cancergenes’).Aftertwodecadesofsearching,howmany
4、havebeenidentifiedandhowdotheycomparetothecompletegenesetthathasbeenrevealedbythehumangenomesequence?Wehaveconducteda‘census’ofcancergenesthatindicatesthatmutationsinmorethan1%ofgenescontributetohumancancer.Thecensusillustratesstrikingfeaturesinthetypesofse
5、quencealteration,cancerclassesinwhichoncogenicmutationshavebeenidentifiedandproteindomainsthatareencodedbycancergenes.NumerousalterationsinDNAsequenceunderliethedevelopmentofeveryneoplasm.Thesesequencevariantscanbetransmittedthroughthegermlineandresultinsus
6、ceptibilitytocancer,orcanarisebysomaticmutation.Acentralaimofcancerresearchhasbeentoidentifythemutatedgenesthatarecausallyimplicatedinoncogenesis(referredtohereas‘cancergenes’).Sincetheadventofrecombinant-DNAtechnologymorethantwodecadesago,therehasbeenconsi
7、derablesuccessinthisenterprise.Followingthefirstreportofasomaticmutationinahumancancergene—theconversionofamino-acid12ofHRASfromglycinetovalineinthehumanbladdercarcinomacelllineT24/EJ1—asubstantialnumberofhumancancergeneshavebeenidentified,andtheirbiologica
8、lpropertieshavebeenassiduouslyinvestigated.Theproteinsthatareencodedbycancergenesnormallyregulatecellproliferation,celldifferentiationandcelldeath.Mutationsunderlyingoncogenesisalsooccuringenesthatmedi