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      • Theses - Department of Molecular Biology and Genetics
      • Dept. of Molecular Biology and Genetics - Master's degree
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      •   BUIR Home
      • University Library
      • Bilkent Theses
      • Theses - Department of Molecular Biology and Genetics
      • Dept. of Molecular Biology and Genetics - Master's degree
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      In silico analysis of mutant p53(R249S) oncogenicity in hepatocellular carcinoma

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      Author
      Ovezmuradov, Guvanchmurad
      Advisor
      Çetin-Atalay, Rengül
      Date
      2007
      Publisher
      Bilkent University
      Language
      English
      Type
      Thesis
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      Abstract
      Oncogenic properties of mutant p53 proteins still stand as an ill-known subject, and the mechanism responsible for this phenomenon remains to be uncovered. This thesis aims to uncover the effect of p53 codon R249S ((AGG→AGT, arginine to serine) mutation on the development of hepatocellular carcinoma (HCC) through high throughput transcriptomics analysis using oligonucleotide arrays. We compared the expression profiles of HepG2 cells carrying wt and mutant p53(R249S). Microarray data analysis revealed a molecular signature consisting of 84 differentially regulated genes, showing that the expression of mutant p53(R249S) in HepG2 cells resulted in a distinct expression profile. Furthermore, mapping these significant differentiallyexpressed genes to the p53 interaction network revealed a putative interaction network representing functional outcomes of p53(R249S) expression in the context of diverse molecular interactions. Our results clearly demonstrated that several Hepatocyte Nuclear Factors (HNF1A, HNF4A and HNF6) could play an essential role in mediating mutant p53 oncogenic activity in HCC, as the key molecules of the gene network.
      Keywords
      p53
      hepatocellular carcinoma
      microarray
      gene network
      bioinformatics
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      http://hdl.handle.net/11693/29985
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      • Dept. of Molecular Biology and Genetics - Master's degree 135
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