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Abnormal Methylation of the Calcitonin Gene in Human Colonic Neoplasms¹

The Oncology Center [S. B. B.] and The Departments of Medicine [A. L. S., S. B. B.] and Pathology [S. R. H.], Johns Hopkins University Medical School, Baltimore, Maryland; NCI-Navy, Medical Oncology Branch [J-G. P., A. F. G.], National Cancer Institute, Bethesda, Maryland; and Department of Medicine [A. L. S., G. D. L.], Wayne State University School of Medicine and Harper Hospital, Detroit, Michigan

Earlier studies of the methylation status of total genomic DNA and of specific genes have demonstrated, predominantly, hypomethylation in human neoplasms. However, we have recently documented the presence of new sites of methylation in the calcitonin gene in human lymphomas (100%), small cell lung carcinomas (92%), and acute myeloid leukemias (95%). We now report that these same novel calcitonin gene methylation sites are also a feature of DNA from human colonic adenomas (13 out of 14 studied), colon carcinomas (4/13), and established colon carcinoma cell lines (18/19), despite the presence of overall genomic DNA hypomethylation in these neoplasms. The data provide further evidence that regional increases in DNA methylation, like gene hypomethylation, occur in benign colonic neoplasms prior to malignant transformation. The fact that abnormalities of calcitonin gene methylation are less frequent in DNA from human colonic carcinomas than from adenomas and colon carcinoma cell culture lines is of special interest. This finding suggests that a more heterogeneous population of cells is present in the carcinomas and that the calcitonin gene hypermethylation may be inherent to cells which are initially selected for growth in culture or are capable of prolonged survival under culture conditions.

¹ This study was supported in part by Grants RO1-CA43280 and CA45831 from the National Cancer Institute, by a grant from the Tobacco Research Council, and by the Clayton Research Fund.

² To whom requests for reprints should be addressed, at Harper Hospital—GI, 3990 John R, Detroit, MI 48201.

Received 4/29/88. Revised 9/16/88. Revised 3/ 6/89. Accepted 4/ 5/89.

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