An Integrated Approach to Uncover Drivers of Cancer

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1、Pleasecitethisarticleinpressas:Akaviaetal.,AnIntegratedApproachtoUncoverDriversofCancer,Cell(2010),doi:10.1016/j.cell.2010.11.013TheoryAnIntegratedApproachtoUncoverDriversofCancerUriDavidAkavia,1,2,5OrenLitvin,1,2,5JessicaKim,3,4FelixSanchez-Garcia,1DylanKotliar,1HelenC

2、.Causton,1PanisaPochanard,3,4EyalMozes,1LeviA.Garraway,3,4andDanaPeer1,2,*1DepartmentofBiologicalSciences,ColumbiaUniversity,1212AmsterdamAvenue,NewYork,NY10027,USA2CenterforComputationalBiologyandBioinformatics,ColumbiaUniversity,1130St.NicholasAvenue,NewYork,NY10032,U

3、SA3DepartmentofMedicalOncology,Dana-FarberCancerInstitute,HarvardMedicalSchool,44BinneyStreet,Boston,MA02115,USA4BroadInstituteofHarvardandMIT,7CambridgeCenter,Cambridge,MA02142,USA5Theseauthorscontributedequallytothiswork*Correspondence:dpeer@biology.columbia.eduDOI10.

4、1016/j.cell.2010.11.013SUMMARYofwhichonlyafewdriveproliferationandmetastasis.Thus,identifyingdrivermutations(geneticchangesthatpromoteSystematiccharacterizationofcancergenomeshascancerprogression)anddistinguishingthemfrompassengersrevealedastaggeringnumberofdiverseaberr

5、ations(thosewithnoselectiveadvantage)hasemergedasamajorthatdifferamongindividuals,suchthatthefunctionalchallengeinthegenomiccharacterizationofcancer.importanceandphysiologicalimpactofmosttumorThemostwidelyusedapproachesarebasedonthefrequencygeneticalterationsremainpoorl

6、ydefined.Wedevel-thatanaberrationoccurs:ifamutationprovidesafitnessadvan-tageinagiventumortype,itspersistencewillbefavored,anditisopedacomputationalframeworkthatintegrateslikelytobefoundinmultipletumors.Forexample,GISTICiden-chromosomalcopynumberandgeneexpressiontifiesregi

7、onsofthegenomethatareaberrantmoreoftenthandatafordetectingaberrationsthatpromotecancerwouldbeexpectedbychanceandhasbeenusedtoanalyzeprogression.Wedemonstratetheutilityofthisanumberofcancers(Beroukhimetal.,2007,2009;Linetal.,frameworkusingamelanomadataset.Ouranalysis2008

8、).However,therearelimitationstoanalyticalapproachescorrectlyidentifiedknowndriversofmelanomaandbasedonCNAdataal