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Exp Clin Endocrinol Diabetes 2005; 113(1): 1-7
DOI: 10.1055/s-2004-830522
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Frequent Promoter Methylation of Tumor-Related Genes in Sporadic and Men2-Associated Pheochromocytomas

R. Dammann[*] 1 , U. Schagdarsurengin1 , C. Seidel1 , C. Trümpler1 , C. Hoang-Vu2 , O. Gimm2 , H. Dralle2 , G. P. Pfeifer3 , M. Brauckhoff[*] 2
  • 1AG Tumorgenetik der Medizinischen Fakultät, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany
  • 2Universitätsklinik und Poliklinik für Allgemein-, Viszeral- und Gefäßchirurgie, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany
  • 3Department of Biology, Beckman Research Institute, City of Hope, Cancer Center, Duarte, California, USA
Further Information

Publication History

Received: November 24, 2003 First decision: March 3, 2004

Accepted: May 3, 2004

Publication Date:
21 January 2005 (online)

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Abstract

Hypermethylation of CpG island promoters is associated with transcriptional inactivation of tumor suppressor genes in neoplasia. Inactivation of p16 and Pten was related to the development of pheochromocytomas. In this report, we investigated the methylation status of the p16INK4a cell cycle inhibitor gene and other prominent tumor-related genes (PTEN, RASSF1 A, CDH1, MSH2, MLH1, VHL, and TIMP3) in sporadic and multiple endocrine neoplasia type 2 (MEN2) pheochromocytomas by methylation-specific PCR. Hypermethylation was detected in 48 % of pheochromocytomas for RASSF1 A, 24 % for p16, 36 % for MSH2, 16 % for CDH1, and 8 % for PTEN. No VHL, MLH1, and TIMP3 methylation was observed. Interestingly, the frequency of p16 inactivation in familial tumors was higher (5 out of 12, 42 %) than in sporadic tumors (1 out of 13, 8 %; p = 0.047) and RASSF1 A inactivation was more common in the hereditary tumors (58 %) compared to the sporadic tumors (38 %). Combined methylation of RASSF1 A and p16 was found only in MEN2-related pheochromocytomas. Thus, a subset of hereditary pheochromocytomas displays preferential methylation of p16 and RASSF1 A.

Key words

Pheochromocytoma - multiple endocrine neoplasia type 2 - methylation - tumor suppressor gene

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1 * contributed equally to this work

Dr. Reinhard Dammann

Institut für Humangenetik und Medizinische Biologie
Martin-Luther-Universität Halle-Wittenberg

Magdeburger Straße 2

06097 Halle/Saale

Germany

Phone: + 493455574537

Fax: + 49 34 55 57 42 93

Email: reinhard.dammann@medizin.uni-halle.de