COMBINED ANALYSIS OF MICROSATELLITE INSTABILITY AND K-RAS MUTATION INCREASES DETECTION INCIDENCE OF NORMAL SAMPLES FROM COLORECTAL-CANCER PATIENTS

Microsatellite instability (MI) and K-ras oncogene mutation have been widely used as biomarkers of genetic changes in colorectal cancer (CRC ), Each of these biomarkers was independently found in normal-appearin g colonic mucosa at stages preceding the development of CRC, albeit at a relatively low incidence, To assess the potential value of combined MI and Ei-ras mutation analysis in the detection of normal-appearing colonic mucosa samples taken from patients with CRC, we have chosen to analyze multiple (3-7) normal colonic mucosa samples and the respecti ve colorectal tumor tissues from 20 patients with CRC, As a control, w e have used 54 normal mucosa samples obtained from 9 autopsies of pati ents without CRC, In at least 1 of 5 loci analyzed, MI was found in 8 of 20 patients via analysis of multiple normal-appearing colonic mucos a samples from each patient, Combined analysis of MI and mutant ras al leles in normal-appearing colonic mucosa samples enabled the identific ation of 11 of 20 patients with CRC, None of the 53 normal colonic muc osa samples obtained from 9 patients without CRC mere found to carry m utant ms or MI. The ability to detect 55% of patients with CRC via the analysis of normal mucosa samples provides an important advance in ou r approach toward early detection of individuals who may be at risk to develop this tumor type.