한국인 산발적 진행성 대장암의 유전자변이

Abstract

To elucidate the molecular basis of advanced colorectal cancer in Korean patients, genetic alterations of K-ras, p53 and nm23H1 genes in primary calorectal cancer tissues were studied. Eighty tumors and it's adjacent mucosa were examined for mutations on K-ras codon 12 by the method of RFLP analysis using specifically designed primers. K-ras codon 12 mutations were observed in 25% (20/80) of tumors examined. We have examined 30 cases of human colorectal cancers for the presence of p53 gene mutations in exon 5, 7 and 8 of the p53 gene by single stranded conformation polymorphysm and restriction fragment length polymorphysm analysis. Surprisingly, mutation rats of p53 gene was low in mutational hot spots. In addition, there were silent mutations in exon 8 (codon 273). To gain some informations on the biologic progression of metastatic colorectal cancer, we have investigated nm23H1 gene by slot blot. PCR-SSCP and PCR-RFLP methods. Fifteen % (3 of 20) of them exibited suspicious mutation of nm23H1 gene. whereas in 3 of the 10 colon neoplasms. the nm23 expression was further increased in cancer tissues when compared with it's adjacent mucosa. This study suggests different rate of gene mutation between Korea and western countries, therefore p53 hot spots(codon 175, 248, 273) may not be useful for the genetic diagnosis and gene therapy purposed. Further studies are needed to obtain informations regarding the relationship between advanced colorectal tumor and their genetic behavior.