DNA Hypomethylation Affects Cancer-Related Biological Functions and Genes Relevant in Neuroblastoma Pathogenesis 英文参考文献.docVIP

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DNA Hypomethylation Affects Cancer-Related Biological Functions and Genes Relevant in Neuroblastoma Pathogenesis 英文参考文献.doc

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DNA Hypomethylation Affects Cancer-Related Biological Functions and Genes Relevant in Neuroblastoma Pathogenesis 英文参考文献

DNAHypomethylationAffectsCancer-RelatedBiological FunctionsandGenesRelevantinNeuroblastoma Pathogenesis GemmaMayol1,Jose′ I.Mart?′n-Subero2,Jose′ R?′os3,4,AnaQueiros2,MartaKulis5,MarionaSun?ol6, ManelEsteller7,8,9,SoledadGo′mez1,IdoiaGarcia1,CarmendeTorres1,EvaRodr?′guez1,PatriciaGalva′n1, JaumeMora1,CinziaLavarino1* 1Developmental Tumor Biology Laboratory, Hospital Sant Joan de De′u, Fundacio′n Sant Joan de De′u, Barcelona, Spain, 2Department of Anatomic Pathology, PharmacologyandMicrobiology,UniversityofBarcelona,Barcelona,Spain,3LaboratoryofBiostatisticsandEpidemiology,UniversitatAuto`nomadeBarcelona,Barcelona, Spain,4ClinicalPharmacologyService,IDIBAPS,HospitalClinic,Barcelona,Spain,5HematopathologyUnit,HospitalClinic,Barcelona,Spain,6DepartmentofPathology, HospitalSantJoandeDe′u,Barcelona,Spain,7CancerEpigeneticsandBiologyProgram(PEBC),BellvitgeBiomedicalResearchInstitute(IDIBELL),L’Hospitalet,Barcelona, Spain,8DepartmentofPhysiologicalSciencesII,SchoolofMedicine,UniversityofBarcelona,Barcelona,Spain,9Institucio′ CatalanadeRecercaiEstudisAvanc?ats(ICREA), Barcelona,Spain Abstract Neuroblastoma(NB)pathogenesishasbeenreportedtobecloselyassociatedwithnumerousgeneticalterations.However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation.Remarkably,suchhypomethylationaffectedcancer-relatedbiologicalfunctionsandgenesrelevanttoNB pathogenesissuchasCCND1,SPRR3,BTC,EGFandFGF6.Inparticular,differentialmethylationinCCND1affectedmostlyan evolutionary conserved functionally relevant 39 untranslated region, suggesting that hypomethylation out