Reanalysis of RNA-Sequencing Data Reveals Several Additional Fusion Genes with Multiple Isoforms 英文参考文献.docVIP

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Reanalysis of RNA-Sequencing Data Reveals Several Additional Fusion Genes with Multiple Isoforms 英文参考文献.doc

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Reanalysis of RNA-Sequencing Data Reveals Several Additional Fusion Genes with Multiple Isoforms 英文参考文献

ReanalysisofRNA-SequencingDataRevealsSeveral AdditionalFusionGeneswithMultipleIsoforms SaraKangaspeska*,SusanneHultsch,HenrikEdgren,DanielNicorici¤,AstridMuruma¨gi,OlliKallioniemi InstituteforMolecularMedicineFinland(FIMM),Helsinki,Finland Abstract RNA-sequencingandtailoredbioinformaticmethodologieshavepavedthewayforidentificationofexpressedfusiongenes fromthechaoticgenomesofsolidtumors.WehaverecentlysuccessfullyexploitedRNA-sequencingforthediscoveryof24 novelfusiongenesinbreastcancer.Here,wedemonstratetheimportanceofcontinuousoptimizationofthebioinformatic methodologyforthispurpose,andreportthediscoveryandexperimentalvalidationof13additionalfusiongenesfromthe samesamples.IntegrationofcopynumberprofilingwiththeRNA-sequencingresultsrevealedthatthemajorityofthegene fusions were promoter-donating events that occurred at copy number transition points or involved high-level DNA- amplifications. Sequencing of genomic fusion break points confirmed that DNA-level rearrangements underlie selected fusiontranscripts.Furthermore,asignificantportion(.60%)ofthefusiongeneswerealternativelyspliced.Thisillustrates the importance of reanalyzing sequencing data as gene definitions change and bioinformatic methods improve, and highlightsthepreviouslyunforeseenisoformdiversityamongfusiontranscripts. Citation:KangaspeskaS,HultschS,EdgrenH,NicoriciD,Muruma¨giA,etal.(2012)ReanalysisofRNA-SequencingDataRevealsSeveralAdditionalFusionGenes withMultipleIsoforms.PLoSONE7(10):e48745.doi:10.1371/journal.pone.0048745 Editor:JanetShipley,TheInstituteofCancerResearch-London,UnitedKingdom ReceivedFebruary10,2012;AcceptedOctober1,2012;PublishedOctober31,2012 Copyright:?2012Kangaspeskaetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyanAcademyofFinlandPost-DoctoralResearcherGrant(SK)(www.aka.fi),theAcademyofFinlan