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  • Title: Telomerase activity and p53 gene mutation in familial polyposis coli.
    Author: Ikeguchi M, Makino M, Kaibara N.
    Journal: Anticancer Res; 2000; 20(5C):3833-7. PubMed ID: 11268463.
    Abstract:
    BACKGROUND: Familial adenomatous polyposis (FAP) is a dominantly inherited disorder and it is difficult to know when polyps change to carcinoma. In this study, we retrospectively evaluated whether telomerase activity and p53 gene mutations are useful parameters for detecting malignant changes in polyps in patients with FAP. MATERIALS AND METHODS: Twenty-one tissue samples (carcinoma: 5, large polyp: 8, and small polyp: 8) were obtained from 8 patients with FAP. Colorectal carcinomas were detected in 5 patients. As a control, 68 colorectal carcinomas and 11 adenomatous polyps with synchronous colorectal carcinoma from 68 patients and 8 polyps from 8 patients without colorectal carcinoma were obtained. The telomeric repeat amplification protocol (TRAP) assay was used for the detection of telomerase activity. In 21 samples from FAP patients, mutations of exon 5 to 8 in the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method. RESULTS: In 5 patients with FAP who had carcinomas in their colon and rectum, all the samples (carcinomas, large polyps and small polyps) showed telomerase activity. In contrast, in the 3 patients with FAP who had no carcinomas, telomerase activity was not detected in either the large or small polyps. Telomerase activity was detected in 51 out of 68 control colorectal carcinomas (75%) and in 6 out of 19 adenomas (32%). The p53 gene mutation was detected in only 2 carcinomas from 2 patients with FAP and was not detected in any large and small polyps. CONCLUSION: These findings suggest that telomerase is activated before the occurrence of the p53 gene mutation. In FAP, genetic changes associated with the development of colonic adenoma into carcinoma might activate telomerase and such genetic changes might occur in whole polyps of the colon and rectum.
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