[Mutations of APC and K-ras gene in aberrant crypt foci from human colon].
OBJECTIVE
To analyze the mutations of K-ras and APC gene in normal colorectal mucosa, aberrant crypt foci (ACF), adenoma and colorectal carcinoma (CRC); To study the genetic alteration in ACF and its possibility of being a molecular marker of very early colon cancer and to explore the relationship of ACF and colorectal adenoma.


METHODS
DNA from 35 CRC, 15 adenomas, 34 ACF and 15 cases of normal mucosa with mucous glands were isolated by micro-dissection. Direct gene sequencing of k-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene.


RESULTS
Mutation frequency of k-ras gene in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference between the three pathologic changes. The ras gene mutation sites in adenomas, carcinomas and 4 ACF were limited to codon 12 (GGT-->GAT), but in 2 ACF, they were located in codon 13 (GGC-->GAC). K-ras gene mutation in ACF was found more frequently in old patients and in patients with polypoid cancers. No mutations were found in codon 61 in three types of tissue. Mutation rate of APC genes in adenomas and carcinomas was 22.9% (8/35) and 26.7% (4/15) respectively, which was higher than that of ACF 2.9%, (P < 0.05). APC gene mutation in carcinomas was not correlated with age, location, size and differentiation.


CONCLUSIONS
The morphological changes and gene mutation status are different in ACF and adenomas. ACF is a very early morphological lesion in the carcinogenesis of colorectal carcinoma. Therefore, ACF is considered to be the putative "microadenoma" where the development of colorectal carcinomas may be from "normal epithelium to ACF and then to carcinomas".
Yuan
P
P
Department of Pathology, Cancer Hospital, Medical College of Fudan University, Shanghai 200032, China.
Sun
M
M
Zhang
J
J
Zhu
X
X
Shi
D
D
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D017491:Genes, APC; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology