A detailed analysis of K-ras point mutations in relation to tumor progression and survival in colorectal cancer patients.

Point mutations in codon 12, 13, and 61 of the K-ras gene are an early event in tumorigenesis of colorectal cancer, but the impact of number, type, and position of such mutations on the progression of adenomas as well as the clinical behaviour of colorectal carcinomas is not clearly established. A series of 35 adenomas and 117 carcinomas at various stages was subjected to single-strand conformation polymorphism (SSCP) to analyse type, position and number of exon-I K-ras point mutations and to relate the results with patients survival. From our data we conclude that the number of K-ras point mutated tumors shows a trend to increase with tumor progression. The number of multiple K-ras point mutations, however, significantly increases with stage. Most mutations occur in the 1st or 2nd base of codon 12, whereas point mutations in the 3rd base are rare. In adenomas mutations, particularly G-T transversions, in the K-ras gene could indicate a propensity to malignant transformation. G-A transitions and G-C transversions of the second base are associated with metastasized tumors. Regarding survival, patients with K-ras point mutated tumors did worse than their non-mutated counterparts. G-A transitions in the 1st and 2nd base and G-C transversions in the 2nd base were associated with a poor prognosis as compared with G-T transversions in both the 1st and 2nd base. Patient survival therefore is related to the occurrence and type, but not the location, of K-ras point mutations.