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dc.contributor.advisorAkçalı, K. Canen_US
dc.contributor.authorAcun, Tolgaen_US
dc.date.accessioned2016-01-08T18:19:02Z
dc.date.available2016-01-08T18:19:02Z
dc.date.issued2010
dc.identifier.urihttp://hdl.handle.net/11693/15470
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2010.en_US
dc.descriptionThesis (Ph. D.) -- Bilkent University, 2010.en_US
dc.descriptionIncludes bibliographical references leaves 173-199.en_US
dc.description.abstractHepatocellular carcinoma (HCC) is the fifth most-common cancer and the third most common cause of cancer related mortality worldwide. HCC is also the most common type of liver cancer. Hepatocarcinogenesis is a multistep process that is not completely understood until today. In this study, we genetically and epigenetically evaluated candidate genes and molecular pathways which may act in hepatocarcinogenesis. The RAS/RAF/MAPK pathway was genetically investigated and no mutation was described in HCC cell lines for the genes MEK1 (MAP2K1), MEK2 (MAP2K2), ERK1 (MAPK3), ERK2 (MAPK1) and PTP 11 (SHP2). TP53 pathway is also a common target for inactivation during liver carcinogenesis. Our analysis indicated that the presence of the MDM2-SNP309 G allele is inversely associated with the presence of somatic TP53 mutations. This finding suggests that the MDM2-SNP309 G allele may functionally replace TP53 mutations, and in addition to known etiological factors, may be partly responsible for differential HCC prevalence. Epigenetic silencing of SIP1 gene in HCC together with its reduced mRNA and protein level in tumors relative to normal liver tissue indicated SIP1 as a potential tumor suppressor role. Inconsistent with previously published findings in other types of cancers, our results showed for the first time that PTPRD gene is epigenetically downregulated and mutated in liver cancers. Among other candidates our results suggest; FBXL11, TUBA3C, TPTE2, IQSEC1, MIPOL1, CHUK, MCL1, MAGI-2 and PTPRCAP genes are involved in hepatocarcinogenesis.en_US
dc.description.statementofresponsibilityAcun, Tolgaen_US
dc.format.extentxxiii, 224, [3] leaves, illustrationsen_US
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject.lccWI735 .A38 2010en_US
dc.subject.lcshCarcinoma, Hepatocellular.en_US
dc.subject.lcshLiver cancer.en_US
dc.subject.lcshCarcinogenesis.en_US
dc.subject.lcshCancer--Genetic aspects.en_US
dc.titleGenetic and epigenetic evaluation of the candidate genes in human hepatocellular carcinomasen_US
dc.typeThesisen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.publisherBilkent Universityen_US
dc.description.degreePh.D.en_US


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