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Type and Number of Ki-ras Point Mutations Relate to Stage of Human Colorectal Cancer¹

Department of Pathology, University of Limburg, Maastricht and Department of Clinical Chemistry, De Wever Hospital, Heerlen, the Netherlands

Point mutations in the Ki-ras gene belong to the genetic key events in tumorigenesis of colorectal cancer. The type and number of point mutations were detected in specimens from patients with colorectal carcinomas staged as Dukes B and C using single-stranded conformational polymorphism analysis and sequencing. G-A transitions in codon 12 were exclusively found in Dukes B tumors, G-T transversions mainly in Dukes C, and G-C transversions only in Dukes C tumors. Apparently, the G-T and G-C transversions are associated with metastatic behavior of colorectal carcinomas, while G-A transitions are not. In several samples, multiple point mutations could be detected in codon 12, the frequency of multiple mutations increasing with the stage of the tumor.

¹ This study was supported by Grant WS 90-07 from "de Nederlandse Lever Darm Stichting."

² Present address: Department of Immunology, University of Utrecht.

³ To whom requests for reprints should be addressed, at Department of Clinical Chemistry, Dc Wever Hospital, P.O. Box 4446, 6401CX Heerlen, the Netherlands.

Received 4/ 1/94. Accepted 5/17/94.

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