Profile and Frequency of p53 Gene Alterations in Gastritis Lesions from Iran

Abstract

Background: It has been frequently shown that p53 alterations have an important role in the development of gastric cancers but there is no data on p53 alteration in gastric cancer and its precancerous lesions from Iran although this country experiences one of the highest gastric cancer incidence and mortality rates in the world. The purpose of this study was to do a comprehensive assessment of p53 alterations in the Iranian population of gastritis patients and to evaluate the association between p53 alterations, microsatellite status and clinicopathological aspects. Methods: After DNA extraction, PCR sequencing was done for exons 2–7. Also microsatellite status was evaluated using five microsatellite markers: NR-27, NR-21, NR-24, BAT-25 and BAT-26. Results: The highest rate of alteration was seen in codons 72 (85.6%, SNP) and 248 (30.9%, mutation). Also, we found 2 new mutations in codons 9 and 146. In contrast with previous work, transition at the CpG codons was relatively rare. Nucleotide alterations were more prevalent in the Helicobacter pylori-positive group but not significantly. Neither nuclear staining for p53 protein nor microsatellite instability was seen in gastritis lesions. Conclusion: p53 alterations might contribute to the pathogenesis of gastritis and perhaps gastric cancer in Iran. However, the different spectrum seen here implies other mechanism(s) in gastritis and gastric cancer development in the Iranian population.

Correlation between global genome methylation and mutation at CpG codons of p53 gene

“…Ultimately, our previous work on gastritis showed that the CG to TA transition was relatively rare in CpG codons of the p53 gene, which was contrary to the findings of other work . We attributed this phenomenon to DNA hypomethylation in the body of p53 gene because the rate of deamination of cytosine is considerably less than methylated cytosine.…”

“…GC → AT transition in the p53 gene is commonly seen in gastric carcinoma, and transition in the CpG dinucleotides accounts for more than half of GC → AT mutations . However, in our previous work on gastritis, we found that CpG codons 9, 245 and 248 underwent GC → TA transversion, so our hypothesis suggesting the global hypomethylation of the genome during gastritis development encouraged us to assess the probable correlation between global genome hypomethylation and alterations at CpG codons of the p53 gene.…”

“…All samples expressed p53 and mismatch repair proteins (MLH1, MSH2 and MSH6). Also, most patients (89%) were Helicobacter pylori positive …”

“…To search for nucleotide alterations at codons 9, 245 and 248 of the p53 gene, PCR sequencing was carried out using primers and programs (Table ) as previously described . Briefly, PCR was carried out using 1.5 mmol/L magnesium chloride, 10 pmol of each primer, 200 μmol/L of each dNTP and 0.5 unit of Taq polymerase.…”