Related Experiment Video
Updated: Aug 26, 2025
06:27
A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
544
A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation
Connor Yanchus1,2, Kristen L Drucker3, Thomas M Kollmeyer3
1Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Science (New York, N.Y.)
|October 6, 2022
Summary
A common genetic variant, rs55705857, significantly increases the risk of developing isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG). This polymorphism affects gene expression, driving glioma development and impacting nearly half of LGG patients.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Establishing causal links between inherited genetic variations and cancer risk is complex.
- The single-nucleotide polymorphism rs55705857 is strongly associated with increased risk for isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG).
Purpose of the Study:
- To identify the causal genetic variant for IDH-mutant LGG risk.
- To elucidate the molecular mechanisms by which rs55705857 contributes to glioma development.
Main Methods:
- Genomic analysis to pinpoint the causal variant.
- Functional studies in cell lines and a mouse model to investigate molecular pathways.
- Assessing the impact of the risk allele on enhancer activity and gene expression.
Main Results:
- rs55705857 was confirmed as the causal variant for IDH-mutant LGG.
- The risk allele disrupts transcription factor binding at a brain-specific enhancer, leading to increased MYC expression.
- In a mouse model, mutating the rs55705857 locus accelerated LGG development and increased tumor penetrance.
Conclusions:
- rs55705857 drives LGG development through altered gene regulation.
- This study reveals a key mechanism for heritable predisposition to glioma, relevant to approximately 40% of LGG patients.
