A cluster of genes located in Ip36 are down-regulated in neuroblastomas with poor prognosis, but not due to CpG island methylation

Background: A common feature of neuroblastoma tumours are partial deletions of the short arm of chromosome I (Ip-deletions). This is indicative of a neuroblastoma tumour suppressor gene being located in the region. Several groups including our have been studying candidate neuroblastoma genes in the region, but no gene/genes have yet been found that fulfil the criteria for being a neuroblastoma tumour suppressor. Since frequent mutations have not been detected, we have now analyzed the expression and promoter CpG island methylation status of the genes UBE4B, KIFIB, PGD, APITDI, DFFA and PEXI4 in the Ip36.22 region in order to find an explanation for a possible down-regulation of this region. Results: The current study shows that gene transcripts in high stage neuroblastoma tumours are significantly down-regulated compared to those in low stage tumours in the Ip36.22 region. CpG island methylation does not seem to be the mechanism of down-regulation for most of the genes tested, since no methylation was detected in the fragments analyzed. One exception is the CpG island of APITDI. Methylation of this gene is also seen in blood from control individuals and is therefore not believed to participate in tumour development. Conclusion: The genes UBE4B, KIFIB, PGD, APITDI, DFFA and PEXI4 are down-regulated in high stage NB tumours, a feature that can not be explained by CpG island methylation.