Exon-Level Transcriptome Profiling in Murine Breast Cancer Reveals Splicing Changes Specific to Tumors with Different Metastatic Abilities 英文参考文献.docVIP

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Exon-Level Transcriptome Profiling in Murine Breast Cancer Reveals Splicing Changes Specific to Tumors with Different Metastatic Abilities 英文参考文献.doc

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Exon-Level Transcriptome Profiling in Murine Breast Cancer Reveals Splicing Changes Specific to Tumors with Different Metastatic Abilities 英文参考文献

Exon-LevelTranscriptomeProfilinginMurineBreast CancerRevealsSplicingChangesSpecifictoTumorswith DifferentMetastaticAbilities AmandineBemmo1,5*,ChristelDias1,AprilA.N.Rose2,CaterinaRusso2,PeterSiegel2,3,4 ,Jacek Majewski1,5 1DepartmentofHumanGenetics,McGillUniversity,Montreal,Quebec,Canada,2DepartmentofMedicine,McGillUniversity,Montreal,Quebec,Canada,3Departmentof Biochemistry,McGillUniversity,Montreal,Quebec,Canada,4DepartmentofAnatomyandCellBiology,McGillUniversity,Montreal,Quebec,Canada,5McGillUniversity andGenomeQuebecInnovationCenter,Montreal,Quebec,Canada Abstract Background:Breastcanceristhesecondmostfrequenttypeofcanceraffectingwomen.Weareincreasinglyawarethat changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specificallyabouttheinvolvementofalternativesplicingintheformationofmacroscopicmetastases.Ourstudyinvestigates transcriptisoformchangesthatcharacterizetumorsofdifferentabilitiestoformgrowingmetastases. MethodsandFindings:Toidentifyalternativesplicingevents(ASEs)thatareassociatedwiththefullymetastaticphenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic(168FARNand4T07)andhighlymetastatic(4T1)mammarycarcinomas.Statisticalanalysisidentifiedsignificant expressionchangesin7606outof155,994(4%)exonsandin1725outof189,460(1%)intronicregions,whichaffect2623 outof16,654(16%)genes.Thesechangescorrespondtoputativealternativeisoforms—severalofwhicharenovel—that aredifferentiallyexpressedbetweentumorsofvaryingmetastaticphenotypes.Genepathwayanalysisshowedthat1224of genesexpressingalternativeisoformswereinvolvedincellgrowth,cellinteractions,cellproliferation,cellmigrationandcell deathandhavebeenpreviouslylinkedtocancersandgeneticdisorders.WechosetenpredictedsplicevariantsforRT-PCR validation,eightofwhichweresucces