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Non-canonical IDH1 and IDH2 mutations: a clonal and relevant event in an Italian cohort of gliomas classified according to the 2016 World Health Organization (WHO) criteria

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Abstract

According to the 2016 World Health Organization (WHO) classification of tumors of the central nervous system, assessment of exon 4 mutations in isocitrate dehydrogenase 1 or 2 genes (IDH1 or IDH2) is an essential step in the characterization of gliomas. The p.R132H mutation is the most frequent alteration in IDH genes, however other non-canonical IDH mutations can be identified. The aim of this study is to investigate in depth the prevalence of non-R132H IDH (“non-canonical”) mutations in brain tumors classified according to the 2016 WHO scheme and their clonal distribution in neoplastic cells. A total of 288 consecutive cases of brain gliomas (grade II–IV) were analyzed for exon 4 IDH1 and IDH2 mutations. IDH1 and IDH2 analysis was performed using next generation sequencing. Non-canonical IDH mutations were identified in 13/52 (25.0%) grade II gliomas (astrocytomas: 8/31, 25.8%; oligodendrogliomas: 5/21, 23.8%) and in 5/40 (12.5%) grade III gliomas (astrocytomas: 3/25, 12.0%; oligodendrogliomas: 2/15, 13.3%). They were not identified in 196 grade IV gliomas (192 glioblastomas, 4 gliosarcomas). In the large majority (>80%) of tumors IDH mutations, both IDH1-R132H and the non-canonical ones, were present in the large majority (>80%) of neoplastic cells. Our data highlight the importance of investigating not only the IDH1-R132H mutation but also the non-canonical ones. These mutations are clonally distributed, with proportions of mutated neoplastic cells overlapping with those of p.R132H, a finding consistent with their driver role in gliomagenesis.

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Acknowledgements

This work was supported in part by an Italian Government-Ministero Della Salute Grant No. RF-2011-02350857 to G.T.

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  1. Gianluca Marucci

    Present address: Department of Neuropathology, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy

Authors and Affiliations

  1. Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale) - Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, Bologna, Italy

    Michela Visani, Giorgia Acquaviva & Giovanni Tallini

  2. Anatomic Pathology Unit, AUSL of Bologna, Via Altura 3, 40139, Bologna, Italy

    Gianluca Marucci

  3. Department of Oncology, AUSL Bologna - IRCCS Institute of Neurological Sciences, Bologna, Italy

    Alexandro Paccapelo, Antonella Mura, Enrico Franceschi & Alba A. Brandes

  4. Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie) - Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, Bologna, Italy

    Daniela Grifoni, Annalisa Pession & Dario de Biase

  5. Anatomia Patologica, ASL Bologna, Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Scuola di Medicina e Chirurgia, Università di Bologna, Via Altura 3, 40139, Bologna, Italy

    Giovanni Tallini

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Michela Visani and Giorgia Acquaviva cooperated equally to this work.

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Visani, M., Acquaviva, G., Marucci, G. et al. Non-canonical IDH1 and IDH2 mutations: a clonal and relevant event in an Italian cohort of gliomas classified according to the 2016 World Health Organization (WHO) criteria. J Neurooncol 135, 245–254 (2017). https://doi.org/10.1007/s11060-017-2571-0

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  • DOI: https://doi.org/10.1007/s11060-017-2571-0

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