In the course of a program to screen a panel of 22 glioma cell lines by CGH-array using our custom-made BAC/PAC-based array, we identified frequent hemizygous deletion of 13q. Expression array analysis of genes located on 13q revealed that expression of a candidate tumor suppressor gene, TSGL1, is remarkably decreased. Expression of TSGL1 was observed in normal brain tissue, whereas it was frequently decreased or silenced in glioma cell lines (21/22, 95.5%). Because epigenetic mechanisms are important ways of transcriptionally silencing tumor suppressor genes, we examined the role of DNA methylation in the expression of TSGL1 and tested the effect of restored expression of TSGL1 on growth of glioma cells. Silenced TSGL1 expression was restored after treatment with 5-aza-2’-deoxycytidine. Methylation status of the TSGL1 CpG island, which showed promoter activity, was inversely correlated with its expression. Methylation of the TSGL1 CpG island was also observed in primary gliomas (16/53, 30.2%). Restoration of TSGL1 expression in glioma cells reduced colony formation. In addition, immunocytochemical analysis showed that TSGL1 protein is located in cetrosome in the metaphase during mitosis. These results suggest that loss of TSGL1 function, which may be associated with mitosis, often occurs by transcriptional silencing through hypermethylation of its CpG island in gliomagenesis.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]