Hypermethylation of Chromosome 17P Locust D17S5 in Human Prostate Tissue

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Abstract
Under normal conditions genomic CpG islands are not methylated. Hypermethylation of a CpG island in the 5' regulatory region of a gene has the capacity to silence gene transcription. Recently, hypermethylation of a CpG island at D17S5 on chromosome 17P13.3 has been shown to be a frequent tumor-specific event. When it has been observed, hypermethylation of D17S5 occurs solely in neoplastic tissues. Consequently, it has been hypothesized that hypermethylation of D17S5 may be an important carcinogenic event in the organs in which it occurs (colon, kidney, and brain). In this study we examine D17S5 hypermethylation in DNA from the prostate, a gland which is unique in that it undergoes hyperplastic or neoplastic growth or both in virtually all aging men. The methylation sensitive restriction enzyme Notl, a cDNA probe specific for the D17S5 locus, and Southern blotting were used to assay for hypermethylation of D17S5 in DNA derived from normal, benign hyperplastic and malignant prostate tissues. We find that methylation of Notl restriction sites at D17S5 is a very common occurrence in prostate cancers (25 of 26 cases examined). Surprisingly, we found that methylation of these sites at D17S5 also occurred in histologically normal prostate and benign hyperplastic (BPH) tissue from glands which both did and did not contain cancer. In contrast, seminal vesicle, an androgen-dependent male sex accessory tissue that rarely undergoes pathological overgrowth, was devoid of hypermethylation at this locus. CONCLUSIONS. These data demonstrate that hypermethylation of D17S5 is a tissue-specific event in prostate DNA, and we hypothesize that methylation of this and/or related loci may play a role in the extreme predilection of this gland to neoplastic growth.