title: Abundance of LRP12 C-rs9694676 allelic promoter variant in epilepsy-associated gangliogliomas.
abstract: OBJECTIVE
  Chronic epilepsy associated gangliogliomas (GGs) represent tumors composed of irregularly distributed, often dysmorphic, neurons and neoplastic astroglia. The pathogenesis of GGs is largely unknown. Low-density lipoprotein receptor-related protein 12 (LRP12) is critical for brain development and involved in tumorigenesis of non-cerebral neoplasms.
  
  
  METHODS
  Here, we have examined a potential role of LRP12 in the pathogenesis of GGs by a combination of mRNA quantification and molecular-biological in vitro assays.
  
  
  RESULTS
  We observed a significant increase of the single nucleotide polymorphism (SNP) rs9694676 C-allele, located in the LRP12 promoter, in GGs compared to normal control individuals. C-allele expression is correlated with abundant seizure frequency. Expression of LRP12 was lower in GGs than in control brain. In luciferase assays, the C-allele of rs9694676 decreases both, the basal LRP12 core promoter activity and the stimulatory effect of the transcription factor (TF) STAT5a.
  
  
  CONCLUSIONS
  Accumulation of functional promoter-associated allelic variants with impact on the transcriptional regulation of LRP12 provides a new pathomechanism for GGs, i.e. highly differentiated epileptogenic brain tumors.
authors.affiliation: Dept. of Neuropathology/Section for Translational Epilepsy Research, Germany.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Robens
authors.affiliation: Dept. of Neuropathology/Section for Translational Epilepsy Research, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Gembé
authors.affiliation: Dept. of Pathology, University Clinic of Cologne, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Fassunke
authors.affiliation: Dept. of Neuropathology/Section for Translational Epilepsy Research, Germany.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.affiliation: Dept. of Neuropathology/Section for Translational Epilepsy Research, Germany; Dept. of Epileptology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
authors.affiliation: Dept. of Neurosurgery, University of Bonn Medical Center, Bonn, Germany. Electronic address: alexander.grote@gmail.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Grote
mesh_terms: D000483:Alleles; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics*; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D018303:Ganglioglioma / Q000150:complications / Q000235:genetics*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C483993:LRP12 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger
keywords: Development; Dysplastic neuron; Epilepsy; Ganglioglioma; Gene expression; Promoter