title: Evaluation of a functional epigenetic approach to identify promoter region methylation in phaeochromocytoma and neuroblastoma.
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.
authors.affiliation: Department of Medical and Molecular Genetics, Institute of Biomedical Research Cancer Research, UK.
authors.forename: Caroline D E
authors.initials: CD
authors.lastname: Margetts
authors.forename: Mark
authors.initials: M
authors.lastname: Morris
authors.forename: Dewi
authors.initials: D
authors.lastname: Astuti
authors.forename: Dean C
authors.initials: DC
authors.lastname: Gentle
authors.forename: Alberto
authors.initials: A
authors.lastname: Cascon
authors.forename: Fiona E
authors.initials: FE
authors.lastname: McRonald
authors.forename: Daniel
authors.initials: D
authors.lastname: Catchpoole
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robledo
authors.forename: Hartmut P H
authors.initials: HP
authors.lastname: Neumann
authors.forename: Farida
authors.initials: F
authors.lastname: Latif
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D009432:Neural Crest / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*