Signatures of Selection in Fusion Transcripts Resulting From Chromosomal Translocations in Human Cancer 英文参考文献.docVIP

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Signatures of Selection in Fusion Transcripts Resulting From Chromosomal Translocations in Human Cancer 英文参考文献.doc

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Signatures of Selection in Fusion Transcripts Resulting From Chromosomal Translocations in Human Cancer 英文参考文献

SignaturesofSelectioninFusionTranscriptsResulting FromChromosomalTranslocationsinHumanCancer In?igoOrtizdeMend?′bil,Jose′ L.Vizmanos,FranciscoJ.Novo* DepartmentofGenetics,UniversityofNavarra,Pamplona,Spain Abstract Background: The recurrence and non-random distribution of translocation breakpoints in human tumors are usually attributedtolocalsequencefeaturespresentinthevicinityofthebreakpoints.However,ithasalsobeensuggestedthat functionalconstraintsmightcontributetodelimitthepositionoftranslocationbreakpointswithinthegenesinvolved,buta quantitativeanalysisofsuchcontributionhasbeenlacking. Methodology:Wehaveanalyzedtwowell-knownsignaturesoffunctionalselection,suchasreading-framecompatibility andnon-randomcombinationsofproteindomains,onanextensivedatasetoffusionproteinsresultingfromchromosomal translocationsincancer. Conclusions:Ourdataprovidestrongexperimentalsupportfortheconceptthatthepositionoftranslocationbreakpoints inthegenomeofcancercellsisdetermined,toalargeextent,bytheneedtocombinecertainproteindomainsandtokeep anintactreadingframeinfusiontranscripts.Additionally,theinformationthatwehaveassembledaffordsaglobalviewof the oncogenic mechanisms and domain architectures that are used by fusion proteins. This can be used to assess the functionalimpactofnovelchromosomaltranslocationsandtopredictthepositionofbreakpointsinthegenesinvolved. Citation:OrtizdeMend?′bilI,VizmanosJL,NovoFJ(2009)SignaturesofSelectioninFusionTranscriptsResultingFromChromosomalTranslocationsinHuman Cancer.PLoSONE4(3):e4805.doi:10.1371/journal.pone.0004805 Editor:MichaelJ.Pazin,NationalInstituteonAging(NIA),NationalInstitutesofHealth(NIH),UnitedStatesofAmerica ReceivedOctober8,2008;AcceptedJanuary30,2009;PublishedMarch12,2009 Copyright:?2009OrtizdeMend?′biletal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:Thisworkhasbeenfunde