title: Frequent epigenetic inactivation of the chaperone SGNE1/7B2 in human gliomas.
abstract: In a genome-wide screen using DMH (differential methylation hybridization) we have identified a CpG island within the 5' region and untranslated first exon of the secretory granule neuroendocrine protein 1 gene (SGNE1/7B2) that showed hypermethylation in low- and high-grade astrocytomas compared to normal brain tissue. Pyrosequencing was performed to confirm the methylation status of this CpG island in 89 astrocytic gliomas of different malignancy grades and six glioma cell lines. Hypermethylation of SGNE1/7B2 was significantly more frequent in diffuse low-grade astrocytomas as well as secondary glioblastomas and anaplastic astrocytomas as compared to primary glioblastomas. mRNA expression analysis by real-time RT-PCR indicates that SGNE1/7B2 expression is downregulated in astrocytic gliomas compared to white matter samples. Treatment of glioma cells with the demethylating agent 5-aza-2'-deoxycytidine restores the transcription of SGNE1/7B2. Overexpression of SGNE1/7B2 in T98G, A172 and U373MG glioblastoma cells significantly suppressed focus formation and led to a significant increase in apoptotic cells as determined by flow cytometric analysis in T98G cells. In summary, we have identified SGNE1/7B2 as a novel target silenced by DNA methylation in astrocytic gliomas. The high incidence of this alteration and the significant effects of SGNE1/7B2 on the growth and apoptosis of glioblastoma cells provide a first proof for a functional implication of SGNE1/7B2 inactivation in the molecular pathology of gliomas.
authors: Department of Neuropathology, University of Bonn, Bonn, Germany. awaha@uni-bonn.de
authors: Anke
authors: A
authors: Waha
authors: Jörg
authors: J
authors: Felsberg
authors: Wolfgang
authors: W
authors: Hartmann
authors: Jennifer
authors: J
authors: Hammes
authors: Anna
authors: A
authors: von dem Knesebeck
authors: Elmar
authors: E
authors: Endl
authors: Torsten
authors: T
authors: Pietsch
authors: Andreas
authors: A
authors: Waha
mesh_terms: D020121:5' Untranslated Regions; D017209:Apoptosis; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051859:Neuroendocrine Secretory Protein 7B2 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D020121:5' Untranslated Regions; D051859:Neuroendocrine Secretory Protein 7B2; C497678:SCG5 protein, human; D000077209:Decitabine; D001374:Azacitidine