ANALYSIS OF MUTANT K-RAS IN MULTIPLE SITES OF NORMAL APPEARING MUCOSAOF COLORECTAL-CANCER PATIENTS

While 50% of colorectal tumors were found to harbor K-ms codon 12 muta tion, only 18% of the respective patients contain this mutation in the normal appearing tissue when enriched PCR, a sensitive method that en ables detection of one mutant allele in 10(4) normal alleles, is used. To determine whether the lower percentage could be attributed to the low incidence of this mutation or to the method of sampling, we have a nalyzed multiple normal appearing samples obtained from the same patie nt. Of 90 non-neoplastic mucosal samples collected from 20 patients wi th colorectal cancer, K-ras codon 12 mutation was identified in 6 samp les taken from 5 patients. These results indicate that only one or two of the multiple samples contain mutant ras alleles. The presence of m utant ras alleles in the normal appearing tissues did not always corre late with that in the tumor site with respect to its presence and/or t he type of base pair alterations, indicating independent or late event s. While pointing to the importance of proper sampling method, the abi lity to detect ms mutation in normal mucosal tissues suggests it may s erve as a useful biomarker of internal/external exposure which precede colorectal cancer development.