Distinct CpG methylation profiles characterize different clinical groups of neuroblastic tumors.
The hypermethylation of CpG islands within gene promoter regions is an epigenetic phenomenon that is often, but not always, associated with the transcriptional silencing of downstream genes and contributes to carcinogenesis. We have determined the pattern of methylation of several genes involved in distinct biological pathways, including cell proliferation and apoptosis, in neuroblastoma and in the nonmalignant ganglioneuroma. The purpose of this work was to search for epigenetic signatures that could be associated with defined clinical and biological parameters and that, in prospective, could identify specific risk categories among the patients. We have analysed 31 malignant neuroblastoma with or without MYCN amplification and 13 benign ganglioneuroma and we have observed dramatic differences in the methylation pattern of five genes (CASP8, 14.3.3sigma, DeltaN-p73, RASSF1A and DCR2) between these tumors indicating that this phenomenon is not tissue-specific and can be considered as cancer-dependent. Furthermore, the methylation pattern of 14.3.3sigma, RASSF1A and of an intragenic segment of CASP8 was significantly different between MYCN amplified and single copy neuroblastoma suggesting a specific role of epigenetic alterations in aggressive neuroblastoma.
Banelli
Barbara
B
Experimental Oncology C, Istituto Nazionale per la Ricerca sul Cancro, IST-Genova, Largo Rosanna Benzi 10, 16132 Genova, Italy.
Gelvi
Ilaria
I
Di Vinci
Angela
A
Scaruffi
Paola
P
Casciano
Ida
I
Allemanni
Giorgio
G
Bonassi
Stefano
S
Tonini
Gian Paolo
GP
Romani
Massimo
M
D048948:14-3-3 Proteins / Q000235:genetics; D053181:Caspase 8; D020169:Caspases / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D009447:Neuroblastoma / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D015996:Survival Rate; D053319:Tumor Necrosis Factor Decoy Receptors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics
D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C411762:RASSF1 protein, human; D018124:Receptors, Tumor Necrosis Factor; C451501:TNFRSF10D protein, human; C000606460:TP73 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases