Alterations of normal DNA methylation patterns have been reported in various types of human tumors. These alterations are represented by genome wide hypomethylation and by region specific hyper methylation. One commonly hypermethylated region is 17p13.3 (D17S5), the putative site of a tumor suppressor gene. In this study we report that hypermethylation at this locus occurs frequently (33%) in ovarian tumors. We reported previously that loss of chromosome 17 is a common event in serous epithelial ovarian tumors. A correlation of the methylation event and chromosome 17 loss suggests that hypermethylation at D17S5 precedes chromosome 17 loss.
Bibliographical noteFunding Information:
Molecular genetic studies of human malignancies have shown both genetic and epigenetic changes in neoplastic cells. Genetic alterations include inactivation of tumor suppressor genes, activation of proto-oncogenes, a'z and mutations within some DNA repair genes. ~'4 Epigenetic changes are represented by genome wide hypomethylation and regional areas of hypermethylation. 5'6 For example, the short arm of chromosome 17 is a "hot spot" for hypermethylation in a variety of human malignancies. This region has been shown to be consistently hypermethylated in co-Ion, lung, renal, and neural tumors. 79 -Significantly, hy-permethylation of tumor DNA has been shown to occur in chromosomal regions that undergo loss of heterozygosity (LOH), suggesting that a causative link exists between the two phenomena. 5 One possibility is that abnormal methylation of chromosomal regions contributes to the phenomenon of chromosomal instability that characterizes many tumor types. Alternatively, increased methylation specifically at the site of tumor suppressor genes may lead to their functional inactivation as shown for the Wilms' tumor and for retinoblastoma genes, l°'n Finally, a mutagenic role for DNA methylation in tumor formation via deamination of methylcytosine to thymidine also has been proposed. 6 Molecular genetic studies of epithelial ovarian tumors have shown that chromosome 17 is lost frequently, with most losses occurring in serous tumors. 12-20 -It is known that numerous tumor suppressor genes are located on this chromosome and at least two of them, p53 and BrCal, have been implicated in ovarian tumor From the Departments of Pathology and Laboratory Medicine, Obstetrics and Gynecology, and Microbiology and Immunology, and Markey Cancer Center, University of Kentucky Medical Center, Lexington, KY. Accepted for publication July 21, 1994. Supported by NIH-NCI Grant No. RO1 CA 60647-01. Address correspondence and reprint requests to Maura Pieretti, PhD, Department of Pathology and Laboratory Medicine, Markey Cancer Center, University of Kentucky, 800 Rose St, Lexington, KY 40536-0093. Copyright © 1995 by W.B. Saunders Company 0046-8177/95/2604-000755.00/0
- chromosome 17
- ovarian tumors