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Updated: Nov 15, 2025
A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
IDH1 Non-Canonical Mutations and Survival in Patients with Glioma
Enrico Franceschi1, Dario De Biase2, Vincenzo Di Nunno1
1Department of Oncology, AUSL Bologna, 40139 Bologna, Italy.
Background:
Non-canonical mutations of the isocitrate dehydrogenase (IDH) genes have been described in about 20-25% and 5-12% of patients with WHO grade II and III gliomas, respectively. To date, the prognostic value of these rare mutations is still a topic of debate.
Methods:
We selected patients with WHO grade II and III gliomas and IDH1 mutations with available tissue samples for next-generation sequencing. The clinical outcomes and baseline behaviors of patients with canonical IDH1 R132H and non-canonical IDH1 mutations were compared.
Results:
We evaluated 433 patients harboring IDH1 mutations. Three hundred and ninety patients (90.1%) had a canonical IDH1 R132H mutation while 43 patients (9.9%) had a non-canonical IDH1 mutation. Compared to those with the IDH1 canonical mutation, patients with non-canonical mutations were younger (p < 0.001) and less frequently presented the 1p19q codeletion (p = 0.017). Multivariate analysis confirmed that the extension of surgery (p = 0.003), the presence of the 1p19q codeletion (p = 0.001), and the presence of a non-canonical mutation (p = 0.041) were variables correlated with improved overall survival.
Conclusion:
the presence of non-canonical IDH1 mutations could be associated with improved survival among patients with IDH1 mutated grade II-III glioma.
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