Evaluation of a functional epigenetic approach to identify promoter region methylation in phaeochromocytoma and neuroblastoma

The molecular genetics of inherited phaeochromocytoma have received considerable attention, but the somatic genetic and epigenetic events that characterise tumourigenesis in sporadic phaeochromocytomas are less well defined. Previously, we found considerable overlap between patterns of promoter regi...

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Published in:	Endocrine-related cancer Vol. 15; no. 3; pp. 777 - 786
Main Authors:	Margetts, Caroline D E, Morris, Mark, Astuti, Dewi, Gentle, Dean C, Cascon, Alberto, McRonald, Fiona E, Catchpoole, Daniel, Robledo, Mercedes, Neumann, Hartmut P H, Latif, Farida, Maher, Eamonn R
Format:	Journal Article
Language:	English
Published:	England Society for Endocrinology 01-09-2008 BioScientifica
Subjects:	Adrenal Gland Neoplasms - genetics Adrenal Gland Neoplasms - pathology Adult Cell Line, Tumor CpG Islands - genetics DNA Methylation Epigenesis, Genetic - physiology Gene Expression Profiling Genes, Tumor Suppressor Humans Neural Crest - pathology Neuroblastoma - genetics Neuroblastoma - pathology Oligonucleotide Array Sequence Analysis Pheochromocytoma - genetics Pheochromocytoma - pathology Promoter Regions, Genetic Sequence Analysis, DNA - methods
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Summary:	The molecular genetics of inherited phaeochromocytoma have received considerable attention, but the somatic genetic and epigenetic events that characterise tumourigenesis in sporadic phaeochromocytomas are less well defined. Previously, we found considerable overlap between patterns of promoter region tumour suppressor gene (TSG) hypermethylation in two neural crest tumours, neuroblastoma and phaeochromocytoma. In order to identify candidate biomarkers and epigenetically inactivated 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, homeobox A9 (HOXA9) and opioid binding protein (OPCML) were methylated in >10% of phaeochromocytomas (52, 17 and 12% respectively). Two of the genes, epithelial membrane protein 3 (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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	1351-0088 1479-6821
DOI:	10.1677/ERC-08-0072