MUTATIONS OF P53 SUPPRESSOR GENE IN GASTRIC ADENOCARCINOMA

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; cel lular differentiation and apoptosis. Aim: To analyze, at a molecular l evel, the possible alterations of p53 suppressor gene in samples of ga stric cancer and non tumoral mucosa. Material and methods: Tissue samp les of gastric cancer and tumoral gastric mucosa coming from 26 patien ts subjected to a total gastrectomy were analyzed. The mutation of p53 suppressor gene exons 7 to 9 were determined using a conformational p olymorphism analysis in single strands of the gene and indirect sequen cing in some cases. Results: Alterations in p53 gene were found in 77% of tumoral and 19% 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 wi th sequencing data showed that T insertion in codon 260 could translat e three erroneous aminonacids after the mutation and produce a truncat ed protein due to the creation of a stop codon. No associations betwee n alterations of p53 gene and clinical or pathological variables such as age sex, tumor localization, histological type and presence of lymp h node metastases were observed. Conclusions: Mutations of p53 suppres sor gene are frequent in gastric carcinoma.