Clinical research Relationship between codon 249 mutation in exon 7 of p53 gene and diagnosis of hepatocellular carcinoma

Abstract

IntroductionHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC. Heat shock proteins have essential roles in protecting cells from the potentially lethal effects of stress. Among them, HSP70 are often overexpressed in cells of various cancers and have been suggested to contribute to tumourigenesis. p53 mutations in codon 249 have also been identified in HCC.Material and methodsFifty patients with liver disease were enrolled in this study compared to 10 healthy volunteers. The studied patients were divided into 2 groups: group I includes those suffering from HCC, group II includes those suffering from post-hepatitis B and C liver cirrhosis. The presence of p53 gene mutation was detected by DNA extraction from whole blood of patients and controls followed by polymerase chain reaction then restriction fragment length polymorphism (RFLP) analysis of codon 249 of exon 7. We also studied the genotypes of the HSP70 gene by PCR followed by RFLP analysis.ResultsOur results revealed no statistical difference between group I, group II, and the control group as regards exon 7 mutation of the p53 gene. Also the frequency of polymorphic genotypes of HSP70 showed no significant difference between the 3 studied groups.ConclusionsThe present study supports the view that the incidence of point mutation of p53 codon 249 mutations in exon 7 of the p53 gene may not play a role in carcinogenesis of HCC in Egyptian patients. Also, genetic polymorphism in HSP70 was not associated with high risk of future development of HCC.

Genetic alterations in hepatocellular carcinoma: An update

“…The mutation or deletion of the p53 gene, which plays an important role in cell growth, division and apoptosis by acting as a transcription factor or by forming complexes with other proteins, is one of the most frequent genetic changes detected in HCC[116,117]. Strikingly, TP53 mutation rates in HCC vary in different geographic areas, reflecting differences in etiological agents and susceptibility factors[118].…”

“…In contrast, TP53 mutations can occur as a late event in carcinogenesis without a typical mutational pattern in areas with low levels of AFB1 intake[135]. Furthermore, another study showed that TP53 R249S mutations might not play a role in the carcinogenesis of HCC in Egypt, where HCV infections are highly prevalent and are a major risk factor for the development of HCC[117]. Taken together, these findings show that TP53 mutations could play an important role in hepatocarcinogenesis in populations with chronic HBV infections, especially in those exposed to excessive levels of AFB1.…”

Systematic review/Meta-analysis Int7G24A polymorphism (rs334354) and cancer risk

“…However, the mechanism of carcinogenesis, which may be triggered by genetic as well as environmental factors, is still not fully understood [18]. In recent years, many candidate genes have been reported to be involved in cancer susceptibility, including p53 [19], SPINK1 [20], TGF-β [1], and so on.…”

Somatostatin analogues in advanced hepatocellular carcinoma: An updated systematic review and meta-analysis of randomized controlled trials

“…There is currently no effective systemic therapy for advanced HCC except sorafenib [31–33]. The role of octreotide in advanced HCC is still uncertain.…”