No AccessJournal of UrologyInvestigative Urology1 Aug 1996Hypermethylation of Chromosome 17P Locust D17S5 in Human Prostate Tissue Ronald A. Morton, John J. Watkins, Steven G. Bova, Michelle Makos Wales, Stephen B. Baylin, and William B. Isaacs Ronald A. MortonRonald A. Morton , John J. WatkinsJohn J. Watkins , Steven G. BovaSteven G. Bova , Michelle Makos WalesMichelle Makos Wales , Stephen B. BaylinStephen B. Baylin , and William B. IsaacsWilliam B. Isaacs View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)65916-0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: 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. Materials and Methods: 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. Results: 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. References 1 : DNA methylation and cancer. Cancer Res.1986; 46: 461. Google Scholar 2 : Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression. Cancer Cells1991; 3: 383. Google Scholar 3 : Choice of enzymes for mapping based on CpG islands in the human genome. Gene. Anal. Tech. Appl.1992; 9: 80. Google Scholar 4 : CpG islands as gene markers in the human genome. Genomics1992; 13: 1095. Google Scholar 5 : Insights into × chromosome inactivation from studies of species variation, DNA methylation and replication, and vice versa. Genet. Res.1990; 56: 91. Google Scholar 6 : Genomic imprinting, DNA methylation, and cancer. J. Natl. Cancer Inst.1994; 86: 753. Google Scholar 7 : DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell1991; 64: 1123. Google Scholar 8 : High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell1990; 62: 503. Google Scholar 9 : Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells. Cancer Res.1994; 54: 2552. Google Scholar 10 : silencing of the VHL tumor suppressor gene by DNA methylation in renal carcinoma. Proc. Natl. Acad. Sci. U.S.A.1994; 91: 9700. Google Scholar 11 : CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene. Oncogene1993; 8: 1063. Google Scholar 12 : Distinct hypermethylation patterns occur at altered chromosome loci in human lung and colon cancer. Proc. Natl. Acad. Sci. U.S.A.1992; 89: 1929. Google Scholar 13 : Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors. Cancer Res1993; 53: 2719. Google Scholar 14 : DNA hypermethylation is associated with 17p allelic loss in neural tumors. Cancer Res.1993; 53: 2715. Google Scholar 15 : Evidence for a second tumor suppressor gene on 17p linked to high S-phase index in primary human breast carcinomas. Cancer Genet. Cytogenet.1994; 76: 106. Google Scholar 16 : Allelic loss on distal chromosome 17p is associated with poor prognosis in a group of Brazilian breast cancer patients. Br. J. Cancer1994; 69: 754. Google Scholar 17 : p53 activates expression of HIC-1, a new candidate tumor suppressor gene on 17p13.3. Nature Med.1995; 1: 570. Google Scholar 18 : Methods of radical prostatectomy specimen processing: a novel technique for harvesting fresh prostate cancer tissue and review of processing techniques. Mod. Pathol.1993; 6: 201. Google Scholar 19 : Allelic loss of chromosomes 16q and 10q in human prostate cancer. Proc. Natl. Acad. Sci. U.S.A.1990; 87: 8751. Google Scholar 20 : Human chromosome 17 Notl linking clones and their use in long-range restriction mapping of the Miller-Dieker chromosome region (MDCR) in 17p13.3. Genomics1990; 7: 264. Google Scholar 21 : VNTR (variable number of tandem repeats) markers show loss of chromosome 17p sequences in human colorectal carcinomas. Cytogenet. Cell Genet.1988; 48: 167. Google Scholar 22 : Cancer Statistics: 1994. CA Cancer J. Clin.1994; 44: 7. Google Scholar 23 : the prostate: an increasing medical problem. Prostate1990; 16: 39. Crossref, Medline, Google Scholar 24 : The molecular biology, endocrinology, and physiology of the prostate and seminal vesicles. In: . Philadelphia: William B. Saunders1992: 221. chapt. 6. Google Scholar 25 : Genetic alterations in prostate cancer-prognostic implications?. In: Prognostic Factors in Urological Cancers. Edited by . Port Washington, New York: Scholium International, Inc.1993: 84. Google Scholar 26 : Tissue specific methylation patterns and expression of the human apolipoprotein AI gene. J. Biol. Chem.1990; 265: 1010. Google Scholar 27 : Methylation patterns of the human apoA-I/C-III/A-IV gene cluster in adult and embryonic tissues suggest dynamic changes in methylation during development. J. Biol. Chem.1991; 266: 23676. Google Scholar 28 : Extensive genetic alterations in prostate cancer revealed by dual PCR and FISH analysis. Genes Chromosomes Cancer1993; 8: 88. Google Scholar 29 : Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc. Natl. Acad. Sci. U.S.A.1994; 91: 11733. Google Scholar James Buchanan Brady Institute of Urology and The Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.Requests for reprints: Scott Department of Urology, Baylor College of Medicine, 6535 Fannin, F421, Houston, Texas 77030.© 1996 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 156Issue 2August 1996Page: 512-516 Advertisement Copyright & Permissions© 1996 by American Urological Association, Inc.MetricsAuthor Information Ronald A. Morton More articles by this author John J. Watkins More articles by this author Steven G. Bova More articles by this author Michelle Makos Wales More articles by this author Stephen B. Baylin More articles by this author William B. 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Morton et al. (1996) studied this question.