HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jerónimo, C Articles by Sidransky, D Search for Related Content PubMed PubMed Citation Articles by Jerónimo, C Articles by Sidransky, D

Endothelin B receptor gene hypermethylation in prostate adenocarcinoma

¹ Portuguese Oncology Institute, R. Dr. Antonio Bernardino de Almeida, 4200–072 Porto, Portugal
² Ludwig Institute for Cancer Research, Rua Prof- Antonio Prudente, 109-4th Floor, São Paulo, SP, 01509-010, Brasil
³ Head and Neck Cancer Research Division, John Hopkins University, 818 Ross Research Building, 720 Rutland Avenue, 21205 Baltimore, Maryland, USA

Correspondence to:
Dr C Jerónimo, Portuguese Oncology Institute, R. Dr. Antonio Bernardino de Almeida, 4200–072 Porto, Portugal;
cjeronimo{at}hotmail.com Background: Alterations in the methylation patterns of promoter CpG islands have been associated with the transcriptional inhibition of genes in many human cancers. These epigenetic alterations could be used as molecular markers for the early detection of cancer—that is, while potentially curable according to current therapeutic strategies. In prostate cancer, GSTP1 hypermethylation is the most common epigenetic alteration, and can be detected in up to 90% of cases. Thus, screening for methylation of other loci would probably increase the number of primary tumours amenable to screening. Moreover, previous studies have shown that the endothelin B receptor (EDNRB) gene is abnormally methylated in a high proportion of prostate tumours (70%).

Aims: To investigate the potential use of EDNRB gene hypermethylation as a prostate cancer specific marker.

Methods: Methylation specific polymerase chain reaction (MSP) for the promoter region of EDNRB was performed on prospectively collected tissue samples from 48 patients harbouring clinically localised prostate cancer, and in a group of 23 patients with benign prostatic hyperplasia (BPH). Genomic DNA was isolated from the samples and the methylation status was examined in a blinded manner.

Results: EDNRB methylation was found in 40 of 48 of the adenocarcinomas. However, the same alteration was found in the paired normal tissue, and 21 of 23 of the BPH samples were found to harbour EDNRB hypermethylation.

Conclusions: EDNRB hypermethylation at CpG sites upstream of the transcription start site can be detected in a high proportion of prostate adenocarcinomas. However, because this same alteration is also present in normal and hyperplastic tissue, it does not distinguish normal from neoplastic prostate cells, thus precluding its use as a prostate cancer marker.

Keywords: benign prostate hyperplasia; EDNRB; methylation specific polymerase chain reaction; hypermethylation; prostate cancer

Abbreviations: BPH, benign prostatic hyperplasia; MSP, methylation specific polymerase chain reaction; PSA, prostate specific antigen; TURP, transurethral resection of the prostate

This article has been cited by other articles:

				A. S Perry, R. Foley, K. Woodson, and M. Lawler The emerging roles of DNA methylation in the clinical management of prostate cancer. Endocr. Relat. Cancer, June 1, 2006; 13(2): 357 - 377. [Abstract] [Full Text] [PDF]

				Y. Berger, C. C. Bernasconi, and L. Juillerat-Jeanneret Targeting the endothelin axis in human melanoma: combination of endothelin receptor antagonism and alkylating agents. Experimental Biology and Medicine, June 1, 2006; 231(6): 1111 - 1119. [Abstract] [Full Text] [PDF]

				L.-C. Li, P. R. Carroll, and R. Dahiya Epigenetic Changes in Prostate Cancer: Implication for Diagnosis and Treatment J Natl Cancer Inst, January 19, 2005; 97(2): 103 - 115. [Abstract] [Full Text] [PDF]

				J. Gilbert, S. D. Gore, J. G. Herman, and M. A. Carducci The Clinical Application of Targeting Cancer through Histone Acetylation and Hypomethylation Clin. Cancer Res., July 15, 2004; 10(14): 4589 - 4596. [Abstract] [Full Text] [PDF]

				S. Yegnasubramanian, J. Kowalski, M. L. Gonzalgo, M. Zahurak, S. Piantadosi, P. C. Walsh, G. S. Bova, A. M. De Marzo, W. B. Isaacs, and W. G. Nelson Hypermethylation of CpG Islands in Primary and Metastatic Human Prostate Cancer Cancer Res., March 15, 2004; 64(6): 1975 - 1986. [Abstract] [Full Text] [PDF]