Document Details

Document Type : Article In Journal 
Document Title :
Frequent epigenetic inactivation of the SLIT2 gene in gliomas
Frequent epigenetic inactivation of the SLIT2 gene in gliomas
 
Document Language : English 
Abstract : The SLIT family of genes consists of large extracellular matrix-secreted and membrane-associated glycoproteins. The Slits (Slit1–3) are ligands for the repulsive guidance receptors, the robo gene family. The Slit–Robo interactions mediate the repulsive cues on axons and growth cones during neural development. In a recent report, we demonstrated that promoter region CpG island of human SLIT2 was frequently hypermethylated in lung, breast and colorectal tumours and the silenced gene transcript suppressed the malignant phenotype in in vitro assays. In this report we undertook epigenetic, genetic and expression analysis of SLIT2 gene in a large series of gliomas and glioma cell lines. Promoter region CpG island of SLIT2 was found to be methylated in 71% (5/7) of glioma cell lines and was unmethylated in five DNA samples from normal brain tissues. The hypermethylation of the SLIT2 promoter region in glioma cell lines correlated with loss of expression and treatment with the demethylating agent 5-aza-2’-deoxycytidine reactivated SLIT2 gene expression. In primary gliomas, SLIT2 was methylated in 59% (37/63) of tumours analysed. In addition, SLIT2 expression was downregulated in methylated gliomas relative to unmethylated tumour samples, as demonstrated by quantitative real-time RT–PCR. Loss of heterozygosity analysis revealed that SLIT2 methylated gliomas retained both alleles of a microsatellite marker within 100 kb of the SLIT2 gene at 4p15.2. Exogenous expression of SLIT2 in a glioma cell line that was heavily methylated for SLIT2 decreased in vitro colony formation. Our data indicate that SLIT2 is frequently inactivated by promoter region CpG island hypermethylation in gliomas and may be a good candidate for a glioma tumour suppressor gene (TSG) located at 4p15.2. Furthermore, our data suggest that a detailed analysis of both the cancer genome and epigenome will be required to identify key TSGs involved in glioma development. 
ISSN : 1476-5594 
Journal Name : Oncogene 
Volume : 22 
Issue Number : 29 
Publishing Year : 1424 AH
2003 AD 
Article Type : Article 
Added Date : Monday, April 26, 2010 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
فريدة لطيفlatif, Farida InvestigatorDoctorateflatif@hgmp.mrc.ac.uk
أشرف دلولDallol, Ashraf ResearcherDoctorate 

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