Abstract. Loss of heterozygosity (LOH) of the entire chromosome 10 is the most frequent genetic alteration in human glioblastoma (GBM). In addition to PTEN/MMAC1 on 10q23.3, clustering of partial deletion break-points on 10q25.3-26.1 points to a second suppressor locus. The proposed target gene DMBT1 was not confirmed. By somatic deletion mapping of this region, we identified the complementary DNA encoding the human homologue of rat orphan G proteincoupled receptor GPR26. GPR26 is highly expressed in fetal and adult brain, but frequently reduced or absent in glioma cells and biopsies, due to de novo methylation of its 5' CpG island. Silencing of GPR26 was reversed with 5-aza-deoxycytidine and the histone deacetylase inhibitor trichostatin A. Furthermore, overexpression of GPR26 in HEK and in U87 glioma cells increased intracellular cAMP concentration which is considered to induce astrocytic differentiation. Interestingly, we observed concomitant silencing of GPR26 with O 6 -methylguanine-DNA methyl transferase (MGMT), a DNA repair gene co-localized on 10q25.3-26.1 (p=0.0001). We conclude that epigenetic silencing is a common mechanism in malignant gliomas that simultaneously inactivates MGMT and GPR26. The 10q25.3-26.1 region may contain an important epigenetic pathway in brain tumorigenesis.
The Common Instrument Middleware Architecture (CIMA) is being used as a core component of a portal based remote instrument access system being developed as an Australian e-Science project. The CIMA model is being enhanced to use federated Grid storage infrastructure (SRB), and the Kepler workflow system to, as much as possible, automate data management, and the facile extraction and generation of instrument and experimental metadata. The Personal Grid Library is introduced as a user friendly portlet interface to SRB data and metadata, and which supports customisable metadata schemas. An Instrument Instruction Module has been introduced as a CIMA plug-in for instrument control. A virtual instrument portlet provides a simulation of the instrument during a data collection. The system is being further augmented with a tool for collaborative data visualisation and evaluation.
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