Mutant K-ras in apparently normal mucosa of colorectal cancer patients. Its potential as a biomarker of colorectal tumorigenesis.
BACKGROUND
The best way to reduce the incidence of colorectal cancer mortality would be to prevent this cancer. However, none of the biomarkers proposed can accurately identify persons at increased risk of colorectal cancer or those at low risk. As a possible genetic biomarker, K-ras mutations, which are frequently found in colorectal cancers, were analyzed in apparently normal colorectal mucosa.


METHODS
Nonneoplastic mucosa and tumor tissues were collected at surgery from 70 patients with colorectal cancer: one sample each from 50 patients (group A) and multiple samples from the other 20 patients (group B). Mutant K-ras codon 12 was analyzed by the enriched polymerase chain reaction (EPCR), by which one mutant can be detected among 10(3) to 10(4) normal alleles.


RESULTS
Only with the aid of EPCR was mutant K-ras detected in nonneoplastic mucosa of nine patients (18%) in Group A and five patients (25%) in Group B. This increased incidence could be attributed to the multiple tissue sampling. The presence of mutant K-ras in nonneoplastic mucosae was not consistently correlated with that in the tumors. These findings suggest that the mutant K-ras identified in nonneoplastic mucosa actually represents de novo mutations, which may be initiated by different etiologic factors and at different times.


CONCLUSIONS
Mutant K-ras detected in apparently normal mucosa should be a useful biomarker for identifying persons at higher risk of colorectal cancer. Our study also emphasizes the need for improving the method for sample collection to achieve true representation of the colorectal mucosa.
Minamoto
T
T
Biochemistry Division National Cancer Center Research Institute, Tokyo, Japan.
Yamashita
N
N
Ochiai
A
A
Mai
M
M
Sugimura
T
T
Ronai
Z
Z
Esumi
H
H
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D007413:Intestinal Mucosa / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction
D014408:Biomarkers, Tumor