The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas

  • Authors:
    • Jean-Louis Boulay
    • Mihai-Constantin S. Ionescu
    • Balasubramanian Sivasankaran
    • Martin Labuhn
    • Béatrice Dolder-Schlienger
    • Elisabeth Taylor
    • Pier Morin
    • Brian A. Hemmings
    • Maria Maddalena Lino
    • Graham Jones
    • Daniel Maier
    • Adrian Merlo
  • View Affiliations

  • Published online on: November 1, 2009     https://doi.org/10.3892/ijo_00000428
  • Pages: 1123-1131
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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 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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November 2009
Volume 35 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Boulay J, Ionescu MS, Sivasankaran B, Labuhn M, Dolder-Schlienger B, Taylor E, Morin P, Hemmings BA, Lino MM, Jones G, Jones G, et al: The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas. Int J Oncol 35: 1123-1131, 2009
APA
Boulay, J., Ionescu, M.S., Sivasankaran, B., Labuhn, M., Dolder-Schlienger, B., Taylor, E. ... Merlo, A. (2009). The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas. International Journal of Oncology, 35, 1123-1131. https://doi.org/10.3892/ijo_00000428
MLA
Boulay, J., Ionescu, M. S., Sivasankaran, B., Labuhn, M., Dolder-Schlienger, B., Taylor, E., Morin, P., Hemmings, B. A., Lino, M. M., Jones, G., Maier, D., Merlo, A."The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas". International Journal of Oncology 35.5 (2009): 1123-1131.
Chicago
Boulay, J., Ionescu, M. S., Sivasankaran, B., Labuhn, M., Dolder-Schlienger, B., Taylor, E., Morin, P., Hemmings, B. A., Lino, M. M., Jones, G., Maier, D., Merlo, A."The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas". International Journal of Oncology 35, no. 5 (2009): 1123-1131. https://doi.org/10.3892/ijo_00000428