Frequent Amplification of CENPF, GMNN and CDK13 Genes in Hepatocellular Carcinomas 英文参考文献.docVIP

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Frequent Amplification of CENPF, GMNN and CDK13 Genes in Hepatocellular Carcinomas 英文参考文献.doc

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Frequent Amplification of CENPF, GMNN and CDK13 Genes in Hepatocellular Carcinomas 英文参考文献

FrequentAmplificationofCENPF,GMNNandCDK13 GenesinHepatocellularCarcinomas Hye-EunKim1.,Dae-GhonKim2.,KyungJinLee1.,JangGeunSon1,Min-YoungSong1,Young-MiPark1, Jae-JungKim1,Sung-WonCho3,Sung-GilChi4,HyunSubCheong5,HyoungDooShin5,6 ,Sang- WookLee7,Jong-KeukLee1* 1AsanInstituteforLifeSciences,UniversityofUlsanCollegeofMedicine,Seoul,Korea,2DepartmentofInternalMedicine,ChonbukNationalUniversityMedicalSchool andHospital,Chonju,Chonbuk,Korea,3AjouUniversitySchoolofMedicine,Suwon,Korea,4SchoolofLifeSciencesandBiotechnology,KoreaUniversity,Seoul,Korea, 5SNP-genetics,Seoul,Korea,6DepartmentofLifeScience,SogangUniversity,Seoul,Korea,7DepartmentofRadiationOncology,UniversityofUlsanCollegeofMedicine, Seoul,Korea Abstract Genomicchangesfrequentlyoccurincancercellsduringtumorigenesisfromnormalcells.UsingtheIlluminaHumanNS-12 single-nucleotidepolymorphism(SNP)chiptoscreenforgenecopynumberchangesinprimaryhepatocellularcarcinomas (HCCs),weinitiallydetectedamplificationof35genesfromfourgenomicregions(1q21–41,6p21.2–24.1,7p13and8q13– 23).ByintegratedscreeningofthesegenesforbothDNAcopynumberandgeneexpressioninHCCandcolorectalcancer, we selected CENPF (centromere protein F/mitosin), GMNN (geminin, DNA replication inhibitor), CDK13 (cyclin-dependent kinase13),andFAM82B(familywithsequencesimilarity82,memberB)ascommoncancergenes.Eachgeneexhibitedan amplificationfrequencyof,30%(range,20–50%)inprimaryHCC(n=57)andcolorectalcancer(n=12),aswellasinapanel of human cancer cell lines (n=70). Clonogenic and invasion assays of NIH3T3 cells transfected with each of the four amplifiedgenesshowedthatCENPF,GMNN,andCDK13werehighlyoncogenicwhereasFAM82Bwasnot.Interestingly,the oncogenic activity of these genes (excluding FAM82B) was highly correlated with gene-copy numbers in tumor samples (correlationcoefficient,r.0.423),indicatingthatamplificationsofCENPF,GMNN,andCDK13genesaretightlylinkedand coincidentintumors.Furthermore,weconfirmedthatCDK13genecopynumberwassignificantlyassociatedwithclinical onseta