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DNA Alterations in Human Aberrant Crypt Foci and Colon Cancers by Random Primed Polymerase Chain Reaction¹

Institute of Pathology [L. L., T. P. P.] and Department of Biochemistry [B. L.], Case Western Reserve University, Cleveland, Ohio 44106

Colon cancers are the result of the accumulation of multiple genetic alterations. To evaluate the role genomic instability plays during tumor development, we compared DNA fingerprints of 44 aberrant crypt foci (ACF; the earliest identified neoplastic lesion in the colon), 23 cancers, and normal crypts generated by random primers with PCR. The PCR products, separated by PAGE and viewed after silver staining, demonstrate altered fingerprints for 23.3% of the ACF and 95.7% of the cancers. In this first study of human ACF with this approach, the finding of altered DNA fingerprints in these microscopic lesions suggests that genomic instability can occur very early in human colon tumorigenesis.

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