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Microsatellite Instability in Aberrant Crypt Foci from Human Colons¹

Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524 [C. D. H., J. G.], and Institute for Disease Prevention, George Washington University Medical Center, Washington, D.C. 20037 [O. A., Z. T., N. S.]

Aberrant crypt foci (ACF) are distinct microscopic lesions of the colon 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 genes include APC, K-Ras, and those of the DNA mismatch repair system. Some colon cancers with mutations in DNA mismatch repair genes are characterized by genomic instability at simple repeated sequences, also known as microsatellite instability. In this study, we analyzed 19 ACF (20 crypts/focus) and adjoining, microscopically normal colonic mucosa from 10 colon cancer patients for the presence 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 observations support the role of ACF as a precursor to colon cancer and provide some evidence that mutations in DNA mismatch repair genes are early somatic events in colon cancer.

¹ Supported by the American Gastroenterological Association Foundation (J. G.), the Council for Tobacco Research, Inc. Grant SA023 (J. G.), the Elsa U. Pardee Foundation (J. G.), NIH Grant CA-63507 (J. G.), and the Cancer Research Foundation of America (N. S.).

² To whom requests for reprints should be addressed, at The George Washington University Medical Center, Suite 421, Ross Hall, 2300 I Street N.W., Washington, DC 20037. Phone: (202) 994-2325; Fax: (202) 994-2297.

Received 8/19/96. Accepted 10/17/96.

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