Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models DOI Creative Commons
Ashley V. Schwartz, Grace F. Chao, Mikella Robinson

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108477 - 108477

Published: April 1, 2025

Mutations in isocitrate dehydrogenase 1 (IDH1) impart a neomorphic reaction that produces D-2-hydroxyglutarate (D2HG), which can inhibit DNA demethylases to drive tumorigenesis. affect residue R132 and display distinct catalytic profiles for D2HG production. We show efficiency of production is greater IDH1 R132Q than R132H mutants, expression cellular xenograft models leads higher concentrations cells, tumors, sera compared R132H. Though hypermethylation damage pathways, hypomethylation more notable when expression. Transcriptome analysis shows increased many pro-tumor pathways upon versus R132H, including transcripts EGFR PI3K signaling pathways. Thus, mutants appear modulate levels via altered catalysis are associated with epigenetic transcriptomic consequences, appearing be aggressive tumors.

Language: Английский

Future Directions in the Treatment of Low-Grade Gliomas DOI
Connor J. Kinslow, Minesh P. Mehta

The Cancer Journal, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

Abstract There is major interest in deintensifying therapy for isocitrate dehydrogenase–mutant low-grade gliomas, including with single-agent cytostatic dehydrogenase inhibitors. These efforts need head-to-head comparisons proven modalities, such as chemoradiotherapy. Ongoing clinical trials now group tumors by intrinsic molecular subtype, rather than classic risk factors. Advances imaging, surgery, and radiotherapy have improved outcomes gliomas. Emerging biomarkers, targeted therapies, immunotherapy, radionuclides, novel medical devices are a promising frontier future treatment. Diverse representation glioma research will help to ensure that advancements care realized all groups.

Language: Английский

Citations

0
Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models DOI Creative Commons
Ashley V. Schwartz, Grace F. Chao, Mikella Robinson

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108477 - 108477

Published: April 1, 2025

Mutations in isocitrate dehydrogenase 1 (IDH1) impart a neomorphic reaction that produces D-2-hydroxyglutarate (D2HG), which can inhibit DNA demethylases to drive tumorigenesis. affect residue R132 and display distinct catalytic profiles for D2HG production. We show efficiency of production is greater IDH1 R132Q than R132H mutants, expression cellular xenograft models leads higher concentrations cells, tumors, sera compared R132H. Though hypermethylation damage pathways, hypomethylation more notable when expression. Transcriptome analysis shows increased many pro-tumor pathways upon versus R132H, including transcripts EGFR PI3K signaling pathways. Thus, mutants appear modulate levels via altered catalysis are associated with epigenetic transcriptomic consequences, appearing be aggressive tumors.

Language: Английский

Citations

0