Enrico Franceschi1, Dario De Biase2, Vincenzo Di Nunno1, Annalisa Pession2, Alicia Tosoni1, Lidia Gatto1, Giovanni Tallini3, Michela Visani3, Raffaele Lodi4, Stefania Bartolini1, Alba Ariela Brandes1. 1. Department of Oncology, AUSL Bologna, 40139 Bologna, Italy. 2. Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie), Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, 40126 Bologna, Italy. 3. Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale), Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, 40126 Bologna, Italy. 4. IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.
Abstract
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.
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 IDH1R132H 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 IDH1R132H 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.
Entities:
Keywords:
IDH1; WHO grade II glioma; WHO grade III glioma; glioma; prognostic factor