The frequency of K-ras gene mutations in colorectal tumours from FAP patients is similar to those in cases of sporadic adenomas and sporadic colorectal carcinomas indicating that the mechanisms involved in their development may be similar.
To examine which is the main pathway, we analyzed point mutations at codon 12 in the c-K-ras 2 gene in 73 colorectal carcinomas, 13 metastatic tumors, 72 adenomas and 30 normal tissues.
Thus, the frequency and sites of K-ras gene mutation in colorectal carcinoma from familial polyposis coli patients are similar to those in cases of sporadic colorectal carcinoma and may not be the first genetic event linked to the tumorigenesis.
The occurrence of K-ras gene point mutations was closely linked to rapid acetylator genotype, although there was no statistical difference of NAT genotypes between the group of patients with colorectal carcinoma and the group of controls.
Using a simple nonradioactive polymerase chain reaction-based technique, we have investigated the possible prognostic significance of point mutations of the K-ras gene in patients with human colorectal carcinomas.
Previous molecular genetics studies of colorectal cancer have identified multiple mutations in the c-K-ras gene (also known as KRAS2) in all phases of its development.
Activating mutations in the c-K-ras gene occur in about 40% of human colorectal carcinomas, yet the role of this oncogene in tumorigenesis is not known.
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.
With this purpose, we have studied the Ki-ras gene in 108 colorectal cancers using archival tissue and epidemiological data from our previous case-control study.
While alterations in APC, p53, and K-ras genes have been characterized between RER+ and RER- colorectal cancers, the status of deleted in colorectal carcinomas (DCC) gene has not been yet.
Western blots used to characterize ras protein patterns in the same cancer/normal pairs have demonstrated that N-ras protein is more highly expressed in colon tissues than H- or K-ras proteins and that N-ras overexpression occurs in almost 70% of colorectal cancers, with or without a concurrent change in electrophoretic mobility of N-ras protein.
These data extend previous findings that point mutation of codon 61 may be an improbable yet possible event leading to activation of c-Ki-ras-2 in colorectal carcinoma.