Mutaciones del gen supresor de tumor p53 en adenocarcinoma gástrico / Mutations of p53 suppressor gene in gastric adenocarcinoma

RESUMO

Background: We have shown numeric alterations such as hyperploidy and hypoploidy with loss of chromosome 17 in primary gastric cancer. This chromosome maps p53 suppressor gene that induces the transcription of genes related to cellular cycle control, DNA synthesis and repair, cellular differentiation and apoptosis. Aim: To analyze, at a molecular level, the possible alterations of p53 suppressor gene in samples of gastric cancer and non tumoral mucosa. Material and methods: Tissue samples of gastric carcinoma and non tumoral gastric mucosa coming from 26 patients subjected to a total gastrectomy were analyzed. The mutation of p53 suppressor gene exons 7 to 9 were determined using a conformational polymorphism analysis in single strands of the gene and indirect sequencing in some cases. Results: Alterations in p53 gene were found in 77 percent of tumoral and 19 percent of non tumoral samples. T insertions in codons 260, 317 and 321, G insertion in codon 328 and G-T transvertion in codon 302 were found. Aminoacid sequence analysis of p53 protein obtained with sequencing data showed that T insertion in codon 260 could translate three erroneous aminoacids after the mutation and produce a truncated protein due to the creation of a stop codon. No associations between alterations of p53 gene and clinical or pathological variables such as age, sex, tumor localization, histological type and presence of Iymph node metastases were observed