Objective: To investigate the role of mutated mismatch repair gene hMSH2 and mutant p53 gene in the carcinogenesis and development of sporadic digestive tract tumors.
Methods: hMSH2 gene in normal and tumor tissue of 30 digestive tract tumor specimens was examined using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) silver staining. The PCR product with an abnormal strand was sequenced directly. Mutant p53 protein in the tumor tissue was analyzed immunohistochemically.
Results: Six patients were identified as having mutated strands, three on hMSH2 exon 1 and three on hMSH2 exon 5. DNA sequencing revealed that all 6 patients had mutated basic groups that led to decrease in function of the hMSH2 protein. Forty percent (12/30) of patients were p53 positive. The frequency of mutated hMSH2 in p53 positive patients (41.7%) was significantly higher than in p53 negative patients (5.6%, P < 0.05).
Conclusion: The mutation of hMSH2 plays an important role in the carcinogenesis and development of digestive tract tumors through stimulating p53 mutation.