MULTIPLE K-RAS CODON-12 MUTATIONS IN CHOLANGIOCARCINOMAS DEMONSTRATED WITH A SENSITIVE POLYMERASE CHAIN-REACTION TECHNIQUE

作者：LEVI S^*; URBANOISPIZUA A; GILL R; THOMAS DM; GILBERTSON J; FOSTER C; MARSHALL CJ

来源：Cancer Research, 1991, 51(13): 3497-3502.

By using a modified polymerase chain reaction strategy, we have devised an approach to detect a K-ras oncogene mutated at codon 12 in the presence of 1000 normal alleles. This is a considerable improvement in sensitivity on previous assays. Application of this assay to 15 cholangiocarcinomas showed that all contained a K-ras mutation at codon 12 and that nine of the tumors contained two or more mutations. In 11 cases, mutations were present in less than 10% of the cells in the sample. In common with pancreatic adenocarcinomas, in which 75 to 95% of cases contain a mutation in K-ras, cholangiocarcinomas show a very high frequency of ras gene mutation, but within a tumor only a fraction of cells contain a ras mutation. The presence of multiple mutations and the low frequency of mutant alleles in the samples argue against K-ras mutations being the initiating genetic lesion in this tumor, but suggest that ras gene mutation is involved in the stepwise progression of neoplastic cells to full malignancy.

• 出版日期1991-7-1