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Evaluation of a functional epigenetic approach to identify promoter region methylation in phaeochromocytoma and neuroblastoma
Margetts, CDE Morris, M Astuti, D Gentle, DC Cascon, A McRonald, FE Catchpoole, D Robledo, M Neumann, HPH Latif, F
Margetts, CDE
Morris, M
Astuti, D
Gentle, DC
Cascon, A
McRonald, FE
Catchpoole, D
Robledo, M
Neumann, HPH
Latif, F
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2008-09-01
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Abstract
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. © 2008 Society for Endocrinology.
Citation
Margetts, C. D. E., Morris, M., Astuti, D., Gentle, D. C., Cascon, A., McRonald, F. E., Catchpoole, D., Robledo, M., Neumann, H. P. H., Latif, F. and Maher, E. R. (2008) Evaluation of a functional epigenetic approach to identify promoter region methylation in phaeochromocytoma and neuroblastoma, Endocrine-Related Cancer, 15(3), pp. 777–786.
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Research Unit
PubMed ID
18499731
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Journal article
Language
en
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ISSN
EISSN
1479-6821
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Sponsors
Cancer Research UK and the University of Birmingham