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IDH mutant high-grade gliomas.

Santosh Valvi1,2,3, Maryam Fouladi4, Michael J Fisher5,6

  • 1Department of Pediatric and Adolescent Oncology and Hematology, Perth Children's Hospital, Perth, WA, Australia.

Frontiers in Molecular Neuroscience
|September 15, 2025
PubMed
Summary

Isocitrate dehydrogenase (IDH) mutations define a distinct glioma subclass with better outcomes. This review covers IDH-mutant gliomas in children and young adults, focusing on biology, diagnosis, treatment, and prognosis.

Keywords:
IDH inhibitorsIDH mutationadolescent and young adultsclinical trialshigh-grade gliomapediatric

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Area of Science:

  • Neuro-oncology
  • Molecular Pathology
  • Cancer Genetics

Background:

  • Gliomas are primary central nervous system (CNS) tumors with high morbidity and mortality, particularly in pediatric and adolescent and young adult (AYA) populations.
  • Isocitrate dehydrogenase (IDH) gene mutations are key drivers in glioma classification, distinguishing tumors with unique clinical and molecular profiles.
  • IDH mutations, while more prevalent in adults, are found in 5-15% of pediatric gliomas, impacting prognosis and treatment response.

Purpose of the Study:

  • To provide a comprehensive review of current knowledge on IDH-mutant high-grade gliomas (HGG).
  • To summarize the biology, clinical features, diagnosis, treatment, and prognosis of IDH-mutant gliomas.
  • To highlight future research and clinical management strategies, with a focus on the AYA cohort.

Main Methods:

  • Literature review of IDH-mutant gliomas.
  • Synthesis of data on molecular characteristics, clinical presentation, and therapeutic outcomes.
  • Analysis of prognostic factors and future research directions.

Main Results:

  • IDH-mutant gliomas exhibit distinct biological and clinical features compared to IDH-wildtype gliomas.
  • These tumors generally show a more favorable prognosis and better response to therapy.
  • The review consolidates current understanding across various aspects of IDH-mutant HGG.

Conclusions:

  • IDH mutation status is a critical determinant in glioma classification and patient outcomes.
  • Understanding IDH-mutant gliomas is essential for advancing treatment strategies, especially in pediatric and AYA patients.
  • Further research is needed to optimize management and improve survival for this specific glioma subtype.