Molecular Genetic and Epigenetic analysis of NCX2/SLC8A2 at 19q13.3 in Human Gliomas
2010 (English)In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 36, no 3, 198-210 p.Article in journal (Refereed) Published
Loss of heterozygosity (LOH) at 19q13.3 is a common genetic change in human gliomas, indicating yet unknown glial-specific tumour suppressor genes in this chromosome region. NCX2/SLC8A2 located on chromosome 19q13.32 encodes a Na(+)/Ca(2+)exchanger, which contributes to intracellular Ca(2+)homeostasis. Its expression is restricted to brain, and it is neither present in other normal tissues nor in gliomas at any significant level. The aim of this study was to investigate if NCX2 might be a tumour suppressor gene involved in glioma.
We performed a systematic analysis of NCX2 in 42 human gliomas using microsatellite analysis for evaluation of LOH at 19q, DNA sequencing and DNA methylation analysis.
Except for three known intragenic SNPs, rs12459087, rs7259674, and rs8104926, no NCX2 sequence variations were detected in any of the tumour samples. Furthermore, a CpG island in the 5' promoter region of NCX2 was unmethylated. Interestingly, the CpG sites of three gene-body CpG islands located in exon 2, intron 2-3 and exon 3 and of a 5' CpG rich area relevant to so called CpG island shore of NCX2 were methylated in all 8 glioma samples and in 3 established glioma cell lines tested. Surprisingly, NCX2 could be activated by addition of the DNA methylation inhibitor 5-aza-2'-deoxycytidine to glioma cell lines in which NCX2 was completely silent.
Results indicate that DNA methylation may play a key role in the transcriptional silencing of NCX2.
Place, publisher, year, edition, pages
2010. Vol. 36, no 3, 198-210 p.
19q13.3, DNA methylation, Glioma, Mutation, NCX2, Single nucleotide polymorphism
Medical and Health Sciences
Research subject Neurology
IdentifiersURN: urn:nbn:se:uu:diva-123034DOI: 10.1111/j.1365-2990.2010.01070.xISI: 000276024600003PubMedID: 20132488OAI: oai:DiVA.org:uu-123034DiVA: diva2:311659