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 colorectal cancer tissues were studied. Eighty tumors and their addjacent mucosa were examined for mutations of 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 strand conformation polymorphism (SSCP) and restriction fragment length polymorphism(RFLP) analysis. Surprisingly, mutation rate of p53 gene was low in mutational got spots. In addition, there were silent mutations in exon 8(codon 273). To gain some information on the biologic progression of metastatic colorectal cancer, we have investigated nm23L1 gene by slot blot, PCR-SSCP and PCE-RFLP methods. The 15% (3 of 20) of them exhibited 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 their 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 genetic diagnosis and gene therapy purposes. Further studies are needed to obtain information regarding the relationship between advanced colorectal tumors and their genetic behavior.