MICROSATELLITE INSTABILITY IN ABERRANT CRYPT FOCI FROM HUMAN COLONS

Aberrant crypt foci (ACP) are distinct microscopic lesions of the colo n thought to be the earliest identifiable precursors of colon cancer. As precursors of colon cancer, ACF may contain mutations in genes that are altered early in colorectal tumorigenesis. Candidates for these g enes include APC, K-Ras, and those of the DNA mismatch repair system. Some colon cancers with mutations in DNA mismatch repair genes are cha racterized by genomic instability at simple repeated sequences, also k nown as microsatellite instability. In this study, we analyzed 19 ACF (greater than or equal to 20 crypts/focus) and adjoining, microscopica lly normal colonic mucosa from 10 colon cancer patients for the presen ce of microsatellite instability. DNA from two ACF from two different patients displayed microsatellite instability. None of the DNA samples from normal mucosa displayed microsatellite instability. These observ ations support the role of ACF as a precursor to colon cancer and prov ide some evidence that mutations in DNA mismatch repair genes are earl y somatic events in colon cancer.