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This Article Accepted manuscript (PDF) Supplementary Data All Versions of this Article: ERC-08-0072v1 15/3/777    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Margetts, C. Articles by Maher, E. Search for Related Content PubMed PubMed Citation Articles by Margetts, C. Articles by Maher, E.

C Margetts, Department of Medical and Molecular Genetics, University of Birmingham School of Medicine, Birmingham, United Kingdom
M Morris, Department of Medical and Molecular Genetics, University of Birmingham School of Medicine, Birmingham, United Kingdom
D Astuti, Department of Medical and Molecular Genetics, University of Birmingham School of Medicine, Birmingham, United Kingdom
D Gentle, Department of Medical and Molecular Genetics, University of Birmingham School of Medicine, Birmingham, United Kingdom
A Cascón, Hereditary Endocrine Cancer Group, Department of Human Genetics, CNIO and CIBERER, Madrid, Spain
F McRonald, Department of Medical and Molecular Genetics, University of Birmingham School of Medicine, Birmingham, United Kingdom
D Catchpoole, The Tumour Bankl, The Children's Hospital at Westmead, NSW, Australia
M Robledo, Hereditary Endocrine Cancer Group, Spanish National Cancer Centre (CNIO), Madrid, Spain
H Neumann, Medizinische Klinik IV, Sektion Präventive Medizin, Universitätsklinikum Freiburg, Freiburg i.Br., 79106, Germany
F Latif, Department of Medical and Molecular Genetics, University of Birmingham School of Medicine, Birmingham, United Kingdom
E Maher, Medical and Molecular Genetics, University of Birmingham, Birmingham, B15 2TT, United Kingdom

Correspondence: Eamonn Maher, Email: e.r.maher{at}bham.ac.uk

Abstract

The molecular genetics of inherited phaeochromocytoma have received considerable attention, but the somatic genetic and epigenetic events that characterize tumourigenesis in sporadic phaeochromocytomas are less well defined. Previously we found considerable overlap between patterns of promoter region tumour suppressor gene hypermethylation in two neural crest tumours, neuroblastoma and phaeochromocytoma. In order to identify candidate biomarkers and epigenetically inactivated tumour suppressor genes (TSGs) in phaeochromocytoma and neuroblastoma, we characterised changes in gene expression in three neuroblastoma cell lines after treatment with the demethylating agent 5-azacytidine. Promoter region methylation status was then determined for 28 genes that demonstrated increased expression after demethylation. Three genes HSP47, HOXA9 and OPCML were methylated in >10% of phaeochromocytomas (52%, 17% and 12% respectively). Two of the genes, EMP3 and HSP47, demonstrated significantly more frequent methylation in neuroblastoma than phaeochromocytoma. These findings extend epigenotype of phaeochromocytoma and identify candidate genes implicated in sporadic phaeochromocytoma tumourigenesis.