APC and K-ras gene mutation in aberrant crypt foci of human colon

AIM To study the genetic alteration in ACF andto define the possibility that ACF may be a veryearly morphological lesion with molecularchanges,and to explore the relationshipbetween ACF and colorectal adenoma evencarcinoma.METHODS DNA from 35 CRC,15 adenomas,34ACF and 10 normal mucus was isolated by meansof microdissection.Direct gene sequencing of K-ras gene including codon 12,13 and 61 as well asthe mutation cluster region(MCR)of APC genewas performed.RESULTS K-ras gene mutation frequency inACF,adenoma and carcinoma was 17.6%(6/34),13.3%(2/15),and 14.3%(5/35)respectively,showing no difference(P>0.05)in K-ras gene mutation among three pathologicprocedures.The K-ras gene mutation inadenoma,carcinoma and 4 ACF restricted incodon 12(GGT→GAT),but the other 2 mutationsfrom ACF located in codon 13(GGC→GAC).K-ras gene mutation was found more frequently inolder patients and patients with polypoidcancer.No mutation in codon 61 was found in thethree tissue types.Mutation rate of APC gene inadenoma and carcinoma was 22.9%(8/35)and26.7%(4/15),which was higher than ACF(2.9%)(P<0.05).APC gene mutation incarcinoma was not correlated with age ofpatients,location,size and differentiation oftumor.CONCLUSION ACF might be a very early morphological lesion in the tumorogenesis ofcolorectal tumor.The morphological feature andgene mutation status was different in ACF andadenoma.ACF is possibly putative“microadenoma”that might be the precursor ofadenoma.In addition,the development of asubgroup of colorectal carcinomas mightundergo a way of“normal epithelium→ACF→carcinomas”.