%0 Journal Article
%T A cluster of genes located in 1p36 are down-regulated in neuroblastomas with poor prognosis, but not due to CpG island methylation
%A Helena Car¨¦n
%A Katarina Ejesk£¿r
%A Susanne Fransson
%A Luke Hesson
%A Farida Latif
%A Rose-Marie Sj£¿berg
%A Cecilia Krona
%A Tommy Martinsson
%J Molecular Cancer
%D 2005
%I BioMed Central
%R 10.1186/1476-4598-4-10
%X 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 1p36.22 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 APITD1. Methylation of this gene is also seen in blood from control individuals and is therefore not believed to participate in tumour development.The genes UBE4B, KIF1B, PGD, APITD1, DFFA and PEX14 are down-regulated in high stage NB tumours, a feature that can not be explained by CpG island methylation.Neuroblastoma (NB) is the most common paediatric solid tumour, responsible for 15% of cancer deaths of childhood. It is a tumour of the postganglionic sympathetic nervous system that develops from immature or dedifferentiated neural crest-derived cells [1]. The distal part of chromosome 1p shows loss of heterozygosity (LOH) in 20¨C40% of NB tumours and has therefore been alleged to contain one or more tumour suppressor genes. We and others have previously analyzed the chromosomal region 1p36.2-3 [2-12] and we have recently focused on the gene region involving the genes: UBE4B-KIF1B-PGD-APITD1-CORT-DFFA-PEX14. These genes have been analyzed for mutations and a few have been found in rare tumours [13-17].In search of tumour suppressor genes, the focus has in the last years moved towards epigenetics and methylation of promoter regions. Methylation of cytosines in CpG-dinucleotides is a common modification in mammalian genomes. Methylated cytosines are more susceptible to deamination, which have lead to an erosion of the number of CpG-dinucleotides. The vast majority of CpGs resides within repetitive elements and is methylated. There are also stretches of DNA rich in CpG that are gene associated, i.e. CpG islands, which are normally unmethylated [18]. Methylation is generally associated with repress
%U http://www.molecular-cancer.com/content/4/1/10