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 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.
Margetts
Caroline D E
CD
Department of Medical and Molecular Genetics, Institute of Biomedical Research Cancer Research, UK.
Morris
Mark
M
Astuti
Dewi
D
Gentle
Dean C
DC
Cascon
Alberto
A
McRonald
Fiona E
FE
Catchpoole
Daniel
D
Robledo
Mercedes
M
Neumann
Hartmut P H
HP
Latif
Farida
F
Maher
Eamonn R
ER
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*