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BACKGROUND: Methylation of cytosines 5’of guanine residues (CpGs) is recognised as an important epigenetic phenomenon that contributes to carcinogenesis.

In this study we have aimed to characterise CpG DNA methylation both at global and gene promoter levels in a panel of 27 neuroblastomas

MATERIALS AND METHODS: Luminescent Methylation Assay (LUMA) was used to measure global DNA methylation levels of the tumors. Global DNA methylation levels were assessed in relation to different clinico-pathological tumor features. A set of 11 tumor suppressor gene promoters: VHL, RASSF1A, PTEN, p14, APC, DAP-K, RARbeta2, NORE1A, DcR2, p73, E-cadherin was assessed for promoter CpG methylation using methylation sensitive pyrosequencing. Promoter methylation values for each of the 11 tumor suppressor promoters were correlated to MYC-N amplification status, tumor stage, high-risk status, 1p deletion and disease outcome.

RESULTS: RASSF1A and DcR2 promoters showed considerably high levels of methylation across the tumor samples whereas VHL, PTEN, p14, APC, DAP-K, RARbeta2, NORE1A, p73 and E-cadherin showed no or only marginal methylation. Significant difference was demonstrated between MYCN amplified and non-amplified neuroblastomas for RASSF1A promoter methlylation.

Considerable variation was observed across the tumors samples in terms of global DNA methylation with some tumors showing hyper while others hypo methylation. No association was established to the various clinico-pathological features.

CONCLUSIONS: Our findings demonstrate that neuroblastomas represent a highly heterogeneous group with regard to global DNA methylation. The tumor suppressor promoters RASSF1A and DcR2 are frequently hypermethylated in this tumor type, providing further evidence for the role of these genes in neuroblastomas.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

American Association for Cancer Research
2007