Instability of X chromosome methylation in aberrant crypt foci of the human colon.

摘要: Aberrant crypt foci (ACF) in the colon have long been thought to be precancerous lesions and therefore monoclonal, but this is unresolved. Eleven ACF were isolated from five female patients. From these ACF, 178 individual aberrant crypts (ACs) obtained assessed for clonality using a method based on X chromosome inactivation of polymorphic X-linked human androgen receptor (HUMARA) gene. Ten found mixtures monoclonal polyclonal types. The HUMARA analysis indicated that almost all lesions. Simultaneously, we investigated K-ras mutations each AC. We seven harbored mutation; strikingly, was concordant ACs single ACF. These results, by contrast results indicate are monoclonal. This discrepancy suggests apparently because de novo methylation active chromosome. To confirm possibility, status male competitive PCR assay. One hundred nineteen eight derived four A total 47 119 (39%) showed six mutation, conclude unstable might an early event carcinogenesis.