IDH1 Non-Canonical Mutations and Survival in Patients with Glioma.

Enrico Franceschi,Dario De Biase,Alba Ariela Brandes,Alicia Tosoni,Vincenzo Di Nunno,Raffaele Lodi,Stefania Bartolini,Michela Visani,Lidia Gatto,Giovanni Tallini,Annalisa Pession

doi:10.3390/diagnostics11020342

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.

Highlights

Molecular assessment represents a milestone for the diagnosis of gliomas
The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors establishes that glioma pathological diagnosis must not leave out molecular examination [1]
Present study,harbouring we aimed to assess the clinical achieved by patients with grade gliomas non-canonical with grade II–III gliomas harbouring non-canonical IDH1 mutations

Summary

Introduction

Molecular assessment represents a milestone for the diagnosis of gliomas. In-depth genomic evaluations provide crucial details about the clinical aggressiveness of tumors and can be used to inform the prognosis of the disease [1,2,3,4,5,6,7,8,9,10].The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors establishes that glioma pathological diagnosis must not leave out molecular examination [1].The integration of objective parameters for diagnosis, such as the assessment of molecular markers, is essential in order to homogenize pathological diagnoses and reduce inter-observer variability. Molecular assessment represents a milestone for the diagnosis of gliomas. In-depth genomic evaluations provide crucial details about the clinical aggressiveness of tumors and can be used to inform the prognosis of the disease [1,2,3,4,5,6,7,8,9,10]. The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors establishes that glioma pathological diagnosis must not leave out molecular examination [1]. The integration of objective parameters for diagnosis, such as the assessment of molecular markers, is essential in order to homogenize pathological diagnoses and reduce inter-observer variability

Objectives

Methods

Discussion

Conclusion