Abstract
p53 alterations have been implicated in the development of many cancers, such as gastric cancer, but there is no evidence of p53 intron alterations in gastritis lesions. The aim of this study was to investigate the p53 intron alterations in gastritis along with p53 and mismatch repair protein expression and microsatellite status. PCR-sequencing was conducted for introns 2-7 on DNA extracted from 97 paired samples of gastritis lesions and normal adjacent tissue. Abnormal accumulation of p53 and mismatch repair proteins was investigated using immunohistochemistry. In addition, microsatellite status was evaluated with reference to five mononucleotide markers. Gastritis cases included 41 males and 56 females in the age range of 15-83 years, 87.6% being H.pylori positive. IVS2+38, IVS3ins16 and IVS7+72 were the most polymorphic sites. Their minor allele frequency values were as follows: 0.38, 0.21 and 0.06, respectively. Samples with GG genotype at IVS2+38 and CT at IVS7+72 had no insertion. Moreover, most of the stable samples (91.9 %) had a G allele at IVS2+38. All of the samples were IHC negative for p53 protein, microsatellite stable and expressed mismatch repair proteins. p53 alterations were prominent in the HP+ group, but without statistical significance. According to our results, some p53 polymorphisms such as IVS2+38, IVS3ins16 and IVS7+72, because of their correlations together or with microsatellite status may contribute to gastritis development. However, so far effects on p53 expression and function remain unclear. Therefore, a comprehensive survey is needed to delineate their biological significance.
Highlights
Background: p53 alterations have been implicated in the development of many cancers, such as gastric cancer, but there is no evidence of p53 intron alterations in gastritis lesions
The human p53 gene is located on the chromosome 17, coding for a protein of about 53 kDa composed of 393 amino acids (Bai et al, 2006). p53 is a DNA-binding protein with transcription regulatory activities and as a tumor suppressor gene is essential for preventing aberrant cell proliferation and maintaining genome integrity following genotoxic stress (Brusa et al, 2003; Brueckl et al, 2004)
Accurate RNA splicing requires the absence of mutations in the cis-acting consensus elements known to be involved in RNA splicing i.e., the conserved sequence at the intron-exon junctions and the branch point (Sogame et al, 2003; Thongsuksai et al, 2010)
Summary
Background: p53 alterations have been implicated in the development of many cancers, such as gastric cancer, but there is no evidence of p53 intron alterations in gastritis lesions. The aim of this study was to investigate the p53 intron alterations in gastritis along with p53 and mismatch repair protein expression and microsatellite status. All of the samples were IHC negative for p53 protein, microsatellite stable and expressed mismatch repair proteins. Conclusions: According to our results, some p53 polymorphisms such as IVS2+38, IVS3ins[16] and IVS7+72, because of their correlations together or with microsatellite status may contribute to gastritis development. P53 is a DNA-binding protein with transcription regulatory activities and as a tumor suppressor gene is essential for preventing aberrant cell proliferation and maintaining genome integrity following genotoxic stress (Brusa et al, 2003; Brueckl et al, 2004). The intron sequences in the p53 have been implicated in the regulation of gene expression and in DNA protein interactions through putative sequences for binding. A sequence in the intron 4 is recognized by p53 intron 4-binding protein and some other consensus sequences which are recognized by transcription factors such as Sp1 (Smith et al, 1996) and through which introns
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