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

摘要

AIM: To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes, and to explore the relationship between ACF and colorectal adenoma even carcinoma.METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed.RESULTS: K-ras gene mutation frequency in ACF, 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 pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT→GAT), but the other 2 mutations from ACF located in codon 13 (GGC→GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P < 0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor.CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative "microadenoma" that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of "normal epithelium→ACF→carcinomas".