Gene Mutations in Advanced Colonic Polyps: Potential Marker Selection for Stool-Based Mutated Human DNA Assays for Colon Cancer Screening

The detection and removal of advanced colonic polyps (ACPs) can help prevent the development of colorectal cancer. A set of DNA mutations known to be associated with colorectal carcinoma was tested against resected ACPs to determine the set's potential utility as a marker panel for ACPs. A sensitive mutation marker panel could be used by stool-based assays that look for mutated human DNA to detect the presence of ACPs. DNA from 32 ACPs ≥ 1.0 cm in diameter was amplified and tested for 19 colorectal cancer-associated DNA mutations and for deletions in BAT-26 (microsatellite instability). One or more mutations were identified by microsequencing in 28 of the 32 ACPs (88%). Mutations were identified in k- ras (59%), APC (33%), and p53 (22%). BAT-26 mutation, a marker for microsatellite instability, was not identified. Stool DNA-based assays that can identify these mutations may significantly increase the identification of patients with potentially premalignant ACPs for evaluation and treatment by colonoscopy.