In silico analysis of mutant p53(R249S) oncogenicity in hepatocellular carcinoma
Author
Ovezmuradov, Guvanchmurad
Advisor
Çetin-Atalay, Rengül
Date
2007Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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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.