A Global View of Cancer-Specific Transcript Variants by Subtractive Transcriptome-Wide Analysis 英文参考文献.docVIP

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A Global View of Cancer-Specific Transcript Variants by Subtractive Transcriptome-Wide Analysis 英文参考文献.doc

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A Global View of Cancer-Specific Transcript Variants by Subtractive Transcriptome-Wide Analysis 英文参考文献

AGlobalViewofCancer-SpecificTranscriptVariantsby SubtractiveTranscriptome-WideAnalysis ChunjiangHe,FangZhou,ZhixiangZuo,HanhuaCheng*,RongjiaZhou* DepartmentofGeneticsandCenterforDevelopmentalBiology,CollegeofLifeSciences,WuhanUniversity,Wuhan,People’sRepublicofChina Abstract Background: Alternative pre-mRNA splicing (AS) plays a central role in generating complex proteomes and influences developmentanddisease.However,theregulationandetiologyofASinhumantumorigenesisisnotwellunderstood. Methodology/Principal Findings: A Basic Local Alignment Search Tool database was constructed for the expressed sequence tags (ESTs) from all available databases of human cancer and normal tissues. An insertion or deletion in the alignment of EST/EST was used to identify alternatively spliced transcripts. Alignment of the ESTs with the genomic sequence was further used to confirm AS. Alternatively spliced transcripts in each tissue were then subtractively cross- screened to obtain tissue-specific variants. We systematically identified and characterized cancer/tissue-specific and alternativelysplicedvariantsinthehumangenomebasedonaglobalview.Weidentified15,093cancer-specificvariantsof 9,989 genes from 27 types of human cancers and 14,376 normal tissue-specific variants of 7,240 genes from 35 normal tissues,whichcoverthemaintypesofhumantumorsandnormaltissues.Approximately70%ofthesetranscriptsarenovel. ThesedatawereintegratedintoadatabaseHCSAS(9/database/human.html,pass.Moreover, weobservedthatthecancer-specificASofbothoncogenesandtumorsuppressorgenesareassociatedwithspecificcancer types.Cancershowsapreferenceintheselectionofalternativesplice-sitesandutilizationofalternativesplicingtypes. Conclusions/Significance:Thesefeaturesofhumancancer,togetherwiththediscoveryofhugenumbersofnovelsplice formsforcancer-associatedgenes,suggestanimportantandglobalroleofcancer-specificASduringhumantumorigenesis. Weadvisetheuseofcancer-specificalternativesplicingasapotentialsourceofnewdiagnostic,