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Section of Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB [S. L., A. U-I., R. G., C. J. M.], and Department of Histopathology, Royal Postgraduate Medical School, Du Cane Road, London W12 0NN [D. M. T., J. G., C. F.], United Kingdom
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.
1 Work in the laboratory of C. J. M. is supported by a grant to the Institute of Cancer Research from the Cancer Research Campaign and Medical Research Council. S. L. was supported by a Cancer Research Campaign Clinical Research Fellowship.
2 To whom requests for reprints should be addressed.
Received 11/ 2/90. Accepted 4/15/91.
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