Abstract 4797: A member of the SLC25 family is epigenetically inactivated in human gliomas and suppresses cell growth in vitro

In a genome-wide screen using DMH (differential methylation hybridization) we have identified a CpG rich fragment upstream of the coding region of a member of the solute carrier family 25 (SLC25) that showed hypermethylation in gliomas compared to normal white matter controls. Pyrosequencing analysis was performed to confirm the methylation status of this gene in 76 gliomas and 7 glioma cell lines. Hypermethylation was detected in 14% of primary glioblastomas, 62% of secondary glioblastomas, 27% of anaplastic astrocytomas, 0.7% low-grade diffuse astrocytomas and in 71% of glioma cell lines. None of three investigated white matter samples showed hypermethylation of the investigated region. Hypermethylation of the SLC25 member was significantly more frequent in secondary glioblastomas compared to primary glioblastomas (P = 0.0066). Furthermore, the investigation of matched low grade and high grade glioma tissues revealed that this hypermethylation was associated with progression. Expression of the SLC25 member was investigated by real-time reverse transcription-PCR and found to be down regulated in primary and secondary glioblastomas as well as in anaplastic and low-grade astrocytomas when compared to white matter and total brain tissue. After treatment of glioma cell lines with 5-aza-2’-deoxycytidine, the transcription was restored. In functional investigations overexpression of exogenous SLC25 family member in glioblastoma cell lines lead to a significant reduction in focus formation. In summary, we describe for the first time the epigenetic silencing of a nuclear encoded member of the mitochondrial transporter family (SLC25) in high grade malignant human brain tumors and provide functional proof for its growth suppressive activity on glioma cells in vitro. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4797. doi:10.1158/1538-7445.AM2011-4797