TY - JOUR
T1 - Distinct CpG methylation profiles characterize different clinical groups of neuroblastic tumors
AU - Banelli, Barbara
AU - Gelvi, Ilaria
AU - Di Vinci, Angela
AU - Scaruffi, Paola
AU - Casciano, Ida
AU - Allemanni, Giorgio
AU - Bonassi, Stefano
AU - Tonini, Gian Paolo
AU - Romani, Massimo
PY - 2005/8/25
Y1 - 2005/8/25
N2 - 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, 14.3.3a, ΔN-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 14.3.3σ, 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.
AB - 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, 14.3.3a, ΔN-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 14.3.3σ, 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.
KW - Ganglioneuroma
KW - Methylation
KW - Methylator phenotype
KW - Neuroblastoma
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U2 - 10.1038/sj.onc.1208722
DO - 10.1038/sj.onc.1208722
M3 - Article
C2 - 16044164
AN - SCOPUS:23944463325
VL - 24
SP - 5619
EP - 5628
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 36
ER -