Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastomas are highly malignant brain tumours; they have been described as one of the most deadly human cancers. Two conceptual classifications of the condition exist: primary (de novo), which does not exhibit prior disease and secondary glioblastoma, which develops from a pre-existing glioma. This study investigates whether GPR26 is differentially transcribed in glioblastoma tissue from patients of different ages, in order to define a candidate genetic marker. The transcriptional profile of GPR26 was compared in nine samples: seven glioblastoma tissues and two normal brain tissues using PCR. Despite GPR26 being present in the glioblastoma tissues, it was not transcribed in any of the four cell lines tested. GPR26 transcription ratios were compared between normal and cancerous samples, also age categories <50 and >60 years were compared. Results suggested differential transcription of GPR26, which is significantly less transcribed in tissues from older patients, implied by a p-value of 0.03. This study has identified GPR26 to be a genetic indicator of primary glioblastoma, suggesting that it could be a suppressor of primary glioblastoma development.
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PMID:GPR26: a marker for primary glioblastoma? 1803 67

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 protein-coupled 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 O6-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.
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PMID:The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas. 1978 67