Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Natl Cancer Inst. 1994 Jul 6;86(13):1007-10.

Detection of K-ras mutation in colonic effluent samples from patients without evidence of colorectal carcinoma.

Author information

  • 1Molecular Carcinogenesis Program, American Health Foundation, Valhala, NY 10595.

Abstract

BACKGROUND:

K-ras gene mutation appears in more than 50% of patients with colon tumors. Both its frequency and early appearance may qualify this mutation as a potential biomarker. To enable early detection of mutant K-ras alleles, we had previously developed a sensitive polymerase chain reaction (PCR)-based assay, i.e., enriched PCR, which enables detection of one mutant K-ras allele present within 10,000 normal alleles. Using the enriched PCR, we were able to detect mutant K-ras alleles in "normal-appearing" colonic mucosa in patients with colorectal cancer.

PURPOSE:

A study was initiated to determine whether mutant K-ras alleles could be identified in colonic effluent samples of patients who may be at risk to develop colorectal cancer.

METHODS:

Over 9 years, colonic effluent samples were collected prior to routine colonoscopy from 39 patients who were apparently free of colorectal cancer. These samples were collected from patients with a family history of colorectal cancer (n = 7), adenomatous polyps (n = 7), previously resected colorectal cancer (n = 5), inflammatory bowel disorders (n = 13), normal colonoscopic examination (n = 6), and familial adenomatous polyposis (n = 1). All of the samples were double coded and analyzed for K-ras gene mutation.

RESULTS:

Of the 39 patients, seven were found to harbor mutant K-ras codon 12 alleles. Mutations were found in patients with a family history of colorectal cancer (three of seven), adenomatous polyps (one of seven), previously resected colorectal carcinoma (two of five), and familial adenomatous polyposis (one of one). In one case, effluent was found to harbor a mutant K-ras allele 4 years before the patient was diagnosed with colorectal cancer.

CONCLUSIONS:

(a) Effluent samples contain enough DNA to be detected with enriched PCR. Such samples may well be representative of the entire colon in general as opposed to a localized area such as that usually analyzed during colonoscopy. (b) K-ras gene mutation can be identified in routinely obtained colonic washings of patients who are at risk of developing colorectal cancer. Such mutations were absent in patients with inflammatory bowel disorders and in those who had undergone normal colonoscopic examinations. Detection of K-ras mutation in colonic washings may assist in identifying patients who may be at high risk for developing adenocarcinoma of the colon.

IMPLICATIONS:

The ability to examine colonic effluents provides a powerful and convenient source of sampling and may be adapted for future large-scale screening.

Comment in

PMID:
8007010
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk