Malignant neoplasms, including colon cancers, are thought to arise from a s
ingle initiated progenitor cell. Aberrant crypt foci (ACF) are putative pre
cursors of at least some colon cancers. The pattern of X chromosomal inacti
vation, which is identified by the differential methylation of a site near
a polymorphic CAG repeat in the androgen receptor gene, was used to determi
ne the clonality status of 11 ACP from eight female patients. Ten of II ACF
were found to be monoclonal aberrations. The eleventh ACF appeared monoclo
nal, but nonrandom inactivation of the X chromosome was also seen in normal
crypts from this patient. These results clearly demonstrate that: (a) a hi
gh percentage of ACF lesions are neoplastic rather than hyperplastic; and (
b) ACF are the earliest identified neoplastic lesions in the colon.