Abundance of LRP12 C-rs9694676 allelic promoter variant in epilepsy-associated gangliogliomas

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 inv...

Full description

Saved in:
Bibliographic Details
Published in:Life sciences (1973) 2016-06, Vol.155, p.70-75
Main Authors: Robens, Barbara K., Gembé, Eva, Fassunke, Jana, Becker, Albert J., Schoch, Susanne, Grote, Alexander
Format: Article
Language:English
Subjects:
Alleles
Brain Neoplasms - complications
Brain Neoplasms - genetics
Development
Dysplastic neuron
Epilepsy
Epilepsy - complications
Epilepsy - genetics
Ganglioglioma
Ganglioglioma - complications
Ganglioglioma - genetics
Gene expression
Humans
Low Density Lipoprotein Receptor-Related Protein-1 - genetics
Promoter
Promoter Regions, Genetic
RNA, Messenger - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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. 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.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2016.01.049