Loss of heterozygosity on chromosome loci 2, 3, 5, 11, 17, and 18 in aberrant crypt foci of human colon / 中华病理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To study the genetic basis of aberrant crypt foci (ACF), which serve as a very early morphological alteration during the development of carcinogenesis by analyzing the loss of heterozygosity (LOH).</p><p><b>METHODS</b>DNA from 35 colorectal carcinomas (CRC) and 34 matched ACF were isolated by microdissection. LOH of microsatellite loci at 18q12, 18q21, 5q12, 5q21, 3p21, 2p16, 17q21, 17q11 and 11p13 was detected by means of ABI-SEQUENCER and GeneScan software was applied for analysis.</p><p><b>RESULTS</b>The rate of LOH in ACF (41.18%) was less than that in carcinoma (68.57%) (P < 0.05). The profile of LOH rates at loci 18q12, 5q12, 3p21, 17q21, 17q11, 11p13 and 2p16 in ACF was similar to that in carcinoma. The LOH frequencies on 18q12, 18q21, 5q12, 5q21, and 3p21 were higher than that on 17q11 and 11p13. However the rate at 18q21 and 5q21 in ACF was much lower than that in the carcinoma (P < 0.05). The co-existing carcinomas displayed more polypoid growth pattern and located more at the sigmoid colon and rectum. LOH in carcinomas did not correlate with the location, size, type of the carcinoma and Duke's stage.</p><p><b>CONCLUSIONS</b>ACF are putative preneoplastic lesions that might represent the earliest morphological lesion with the alteration at molecular genetic level. Our study provides further genetic evidence in the pathogenesis of colorectal carcinomas.</p>