Abstract
INTRODUCTION: Gastric and colorectal adenocarcinomas are prevalent malignancies characterized by mutations in genes such as p53, RAS, and MDM2, which play crucial roles in tumorigenesis and cancer progression. Understanding the specific mutational patterns and their implications in these cancers was essential for identifying potential therapeutic targets. AIM: To identify the nature of mutational disorders in the p53, p21Waf1, RAS and MDM2 genes, depending on the degree of cell differentiation by adenocarcinomas of the gastrointestinal tract. METHODS: Genomic DNA was isolated from 200 samples of stomach tissue and 233 samples of colon and rectum adenocarcinomas. A total of 433 samples, including gastric adenocarcinomas, colon and rectum adenocarcinomas and adjacent tissues, were collected. RESULTS: Genomic DNA was isolated, and mutational analysis of p53, RAS (HRAS, KRAS, NRAS), and MDM2 genes was performed using polymerase chain reaction, gel electrophoresis, and restriction enzyme analysis. The deletion of p53 exon-intron 5-6, as well as HRAS 12 and HRAS 61 mutations, were detected in 78% of poorly differentiated adenocarcinomas. The deletions of p53 exon-intron 7-9 - in 100% of moderately differentiated adenocarcinomas and 50-60% of adjacent tissues. The loss of WAF1 gene expression was registered in almost 90% of poorly differentiated adenocarcinomas and 20% of adjacent tissue samples. The KRAS and NRAS mutations in almost 63.9% of studied colon and rectal samples indicated autonomous cell growth. This explains the aggressive and metastatic growth of tumours and the ineffectiveness of growth factor inhibitors in colorectal cancer. Finding ways to influence specific substitutions in RAS genes could prevent and eliminate uncontrolled invasive tumour growth. CONCLUSION: By identifying specific gene mutations and differences in genetic markers, the study provided insights for the development of targeted diagnostic methods and personalised treatment strategies, ultimately improving the clinical outcomes in the field of oncology.