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

Hypomethylation within the body of the p53 gene, which is normally methylated, has been found in neoplasms. Also, the CG → TA transition was not detected in the CpG codons of the p53 gene in gastritis lesions in Iranian patients. Therefore, an evaluation of the probable correlation between global genome methylation and alteration at CpG codons of p53 gene was needed.

For defining the genotypes of CpG codons, DNA sequencing was performed on 90 paired samples of gastritis and normal tissues. To measure global genome methylation status, the extracted DNA was digested with HpaII (methylation sensitive) and MspI (insensitive). Then, enzymatic digestion was quantitated using Pyrosequencing as peak height. By calculating the HpaII/ MspI peak ratio it is possible to evaluate the methylation level of normal and gastritis tissues.

Codons 9, 245 and 248 underwent a CG → AT transversion but not a CG → TA transition. In addition, the mean methylation level was significantly different between the patients with GG and GT genotypes at codon 245 (P = 0.019).

As CG → AT transversion at codon 245 is associated with global genome methylation, GG hypomethylation may induce different pattern of mutations, for example, C → A instead of C → T at the CpG codons of the p53 gene during gastritis development in Iranian patients.