Amplification and Overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in Medulloblastoma 英文参考文献.docVIP

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Amplification and Overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in Medulloblastoma 英文参考文献.doc

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Amplification and Overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in Medulloblastoma 英文参考文献

AmplificationandOverexpressionofHsa-miR-30b,Hsa- miR-30dandKHDRBS3at8q24.22-q24.23in Medulloblastoma YuanLu1,SarraL.Ryan1,DavidJ.Elliott2,GrahamR.Bignell3,P.AndrewFutreal3,DavidW.Ellison4, SimonBailey1,StevenC.Clifford1* 1NorthernInstituteforCancerResearch,NewcastleUniversity,NewcastleuponTyne,UnitedKingdom,2InstituteofHumanGenetics,NewcastleUniversity,Newcastle upon Tyne, United Kingdom, 3Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom, 4DepartmentofPathology,St.JudeChildren’sResearchHospital,Memphis,Tennessee,UnitedStatesofAmerica Abstract Background: Medulloblastoma is the most common malignant brain tumour of childhood. The identification of critical genes involved in its pathogenesis will be central to advances in our understanding of its molecular basis, and the developmentofimprovedtherapeuticapproaches. Methodology/Principal Findings: We performed aSNP-array based genome-widecopy numberanalysis inmedulloblas- tomacelllines,toidentifyregionsofgenomicamplificationandhomozygousdeletion,whichmayharbourcriticaldisease genes.Aseriesofnovelandestablishedmedulloblastomadefectsweredetected(MYCamplification(n=4),17q21.31high- levelgain(n=1);9p21.1–p21.3(n=1)and6q23.1(n=1)homozygousdeletion).Mostnotably,anovelrecurrentregionof genomicamplificationat8q24.22–q24.23wasidentified(n=2),andselectedforfurtherinvestigation.Additionalanalysisby interphasefluorescenceinsituhybridisation(iFISH),PCR-basedmappingandSNP-arrayrevealedthisnovelamplificationat 8q24.22–q24.23isindependentofMYCamplificationat8q24.21,andisuniquetomedulloblastomainover800cancercell lines assessed from different tumour types, suggesting it contains key genes specifically involved in medulloblastoma development. Detailed mapping identified a 3Mb common minimal region of amplification harbouring 3 coding genes (ZFAT1,LOC286094,KHDRBS3)andtwogenesencodingmicro-RNAs(hsa-miR-30b,hsa-miR-30d).Ofthese,onlyexpressionof hsa-miR-30b, hsa-miR-3