Skip to main content

Characteristics of IDH-mutant gliomas with non-canonical IDH mutation

Journal of Neuro-Oncology volume 151, pages 279–286 (2021)Cite this article

Abstract

Background

Approximately 10% of IDH-mutant gliomas harbour non-canonical IDH mutations (non-p.R132H IDH1 and IDH2 mutations).

Objective

The aim of this study was to analyse the characteristics of non-canonical IDH-mutant gliomas.

Materials and methods

We retrospectively analysed the characteristics of 166 patients with non-canonical IDH mutant gliomas and compared them to those of 155 consecutive patients with IDH1 p.R132H mutant gliomas.

Results

The median age at diagnosis was 38 years in patients with non-canonical IDH mutant gliomas and 43 years in glioma patients with IDH1 p.R132H-mutant tumours. Family history of cancer was more frequent among glioma patients harbouring non-canonical IDH mutations than in patients with IDH1 p.R132H mutations (22.2% vs 5.1%; P < 0.05). Tumours were predominantly localised in the frontal lobe regardless of the type of IDH mutation. Compared to IDH1 p.R132H-mutant gliomas, tumours with non-canonical IDH mutations were more frequently found in the infratentorial region (5.5% vs 0%; P < 0.05) and were often multicentric (4.8% vs 0.9%; P < 0.05). Compared to IDH1 P.R132H-mutant gliomas, tumours with non-canonical IDH1 mutations were more frequently astrocytomas (65.6% vs 43%, P < 0.05), while those with IDH2 mutations were more frequently oligodendrogliomas (85% vs 48.3%; P < 0.05). The median overall survival was similar in patients with IDH1 p.R132H-mutant gliomas and patients with non-canonical IDH-mutant gliomas.

Conclusion

Gliomas with non-canonical IDH mutations have distinct radiological and histological characteristics. The presence of such tumours seems to be associated with genetic predisposition to cancer development.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Yan H, McLendon R, Kos I, Riggins GJ, Reardon D, Velculescu VE et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(8):765–773

    CAS  Article  Google Scholar 

  2. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131(6):803–820

    Article  Google Scholar 

  3. Watanabe T, Vital A, Nobusawa S, Kleihues P, Ohgaki H (2009) Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome. Acta Neuropathol 117(6):653–656

    CAS  Article  Google Scholar 

  4. Bonnet C, Thomas L, Psimaras D, Bielle F, Vauléon E, Loiseau H, Ducray F (2016) Characteristics of gliomas in patients with somatic IDH mosaicism. Acta Neuropathol Commun 4(1):1–8

    Article  Google Scholar 

  5. Picca A, Berzero G, Bielle F, Touat M, Savatovsky J, Polivka M et al (2018) FGFR1 actionable mutations, molecular specificities, and outcome of adult midline gliomas. Neurology 90(23):e2086–e2094

    CAS  Article  Google Scholar 

  6. Hayes J, Yu Y, Jalbert LE, Mazor T, Jones LE, Wood MD et al (2018) Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas. Neuro-Oncology 20(5):632–641

    CAS  Article  Google Scholar 

  7. Tabouret E, Nguyen AT, Dehais C, Carpentier C, Ducray F, Figarella-Branger D (2016) Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort. Acta Neuropathol 132(4):625–634

    Article  Google Scholar 

  8. Weller M, Van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, Wick W (2017) European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 18(6):e315–e329

    Article  Google Scholar 

  9. Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H et al (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372:2499–2508

    CAS  Article  Google Scholar 

  10. Labreche K, Kinnersley B, Berzero G, Di Stefano AL, Rahimian A, Detrait I et al (2018) Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci. Acta Neuropathol 135(5):743–755

    CAS  Article  Google Scholar 

  11. Kyritsis AP, Bondy ML, Rao JS, Sioka C (2010) Inherited predisposition to glioma. Neuro-Oncology 12:104–113

    CAS  Article  Google Scholar 

  12. Jenkins RB, Xiao Y, Sicotte H, Decker PA, Kollmeyer TM, Hansen HM et al (2012) A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation. Nat Genet 44(10):1122–1125

    CAS  Article  Google Scholar 

  13. Meyronet D, Esteban-Mader M, Bonnet C, Joly MO, Uro-Coste E et al (2017) Characteristics of H3 K27M-mutant gliomas in adults. Neuro-Oncology 19(8):1127–1134

    CAS  Article  Google Scholar 

  14. Braunstein S, Raleigh D, Bindra R, Mueller S, Haas-Kogan D (2017) Pediatric high-grade glioma: current molecular landscape and therapeutic approaches. J Neurooncol 134(3):541–549

    CAS  Article  Google Scholar 

  15. Lu VM, McDonald KL (2018) Isocitrate dehydrogenase 1 mutation subtypes at site 132 and their translational potential in glioma. CNS Oncol 7(1):41–50

    CAS  Article  Google Scholar 

  16. Akimoto J, Sasaki H, Haraoka R, Nakajima N, Fukami S, Kohno M (2014) A case of radiologically multicentric but genetically identical multiple glioblastomas. Brain Tumor Pathol 31(2):113–117

    Article  Google Scholar 

  17. Lombardi G, Della Puppa A, Gardiman MP, Rossi S, Candiotto C, Zanatta L et al (2018) Discordance of IDH mutational status between lesions in an adult patient with multifocal glioma. Neuro-Oncology 20(8):1142–1143

    CAS  Article  Google Scholar 

  18. Galuppini F, Opocher E, Tabori U, Mammi I, Edwards M, Campbell B et al (2018) Concomitant IDH wild-type glioblastoma and IDH1-mutant anaplastic astrocytoma in a patient with constitutional mismatch repair deficiency syndrome. Neuropathol Appl Neurobiol 44(2):233–239

    CAS  Article  Google Scholar 

  19. Auré K, Laigle-Donadey F, Kaloshi G, Amiel-Benouaich A, Sanson M (2006) Les gliomes multiples: étude clinique et hypothèses physiopathologiques. Rev Neurol 162(8–9):845–851

    Article  Google Scholar 

  20. Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A et al (2009) Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol 118(4):469–474

    Article  Google Scholar 

  21. Appay R, Tabouret E, Macagno N, Touat M, Carpentier C, Colin C, Uro-Coste E (2018) IDH2 mutations are commonly associated with 1p/19q codeletion in diffuse adult gliomas. Neuro-Oncology 20(5):716–718

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Dr C. Dehais, C. Carpentier, Dr E. Cohen-Jonathan Moyal, Dr D. Larrieu-Cirron, S. Lacomme, Dr D. Lassouarn, Dr M. Sanson, Ida Mabru, C. Boucard, Dr E. Vauleon, Pr F. Chapon, Dr L. Bekaert, Dr C. Adam, Pr O. Chinot, Dr I. Quintin-Roué, Dr N. Desse, Dr Beauchesne Patrick, Pr F. Ghiringhelli, Dr M. Mihai, and the members of the French POLA network.

POLA network: Amiens (C. Desenclos, H. Sevestre), Angers (P. Menei, A. Rousseau), Annecy (T. Cruel, S. Lopez), Besançon (M-I Mihai, A. Petit), Bicêtre (C. Adam, F. Parker), Brest (R. Seizeur, I. Quintin-Roué), Bordeaux (S. Eimer, H. Loiseau), Caen (L. Bekaert, F. Chapon), Clamart (D. Ricard), Clermont-Ferrand (C. Godfraind, T. Khallil), Clichy (D. Cazals-Hatem, T. Faillot), Colmar (C. Gaultier, MC. Tortel), Cornebarrieu (I. Carpiuc, P. Richard), Créteil (W. Lahiani), Dijon (H. Aubriot-Lorton, F. Ghiringhelli), Lille (E. Le Rhun, CA. Maurage), Limoges (EM. Gueye, F. Labrousse), Lyon (F. Ducray, D. Meyronnet), Marseille (D. Figarella-Branger, O Chinot), Montpellier (L. Bauchet, V. Rigau), Nancy (P. Beauchesne, G. Gauchotte), Nantes (M. Campone, D. Loussouarn), Nice (D. Fontaine, F. Vandenbos-Burel), Orléans (C. Blechet, M. Fesneau), Paris (A. Carpentier, C. Dehais, JY Delattre, K. Mokhtari, M. Polivka), Poitiers (S. Milin, M. Wager), Reims (P. Colin, MD. Diebold), Rennes (D. Chiforeanu, E. Vauleon), Rouen (O. Langlois, A. Laquerriere), Saint-Etienne (F. Forest, MJ. Motso-Fotso), Saint-Pierre de la Réunion (M. Andraud, G. Runavot), Strasbourg (B. Lhermitte, G. Noel), Suresnes (AL Di Stéfano, C. Villa), Tours (C. Rousselot-Denis, I. Zemmoura), Toulon (N. Desse), Toulouse (E. Cohen-Moyal, E. Uro-Coste), Villejuif (F. Dhermain).

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Affiliations

  1. Service d’Oncologie Médicale, CHU de Bordeaux- Hôpital Saint André, 33000, Bordeaux, France

    L. Poetsch & C. Bronnimann

  2. Service de Neurochirurgie B, CHU de Bordeaux - Hôpital Pellegrin, 33076, Bordeaux, France

    H. Loiseau

  3. EA 7435 – IMOTION (Imagerie moléculaire et thérapies innovantes en oncologie) Université de Bordeaux, 33076, Bordeaux, France

    H. Loiseau

  4. Institut de Cancérologie de l’Ouest, Centre René Gauducheau, 44800, Saint Herblain, France

    J. S. Frénel

  5. Service de Pathologie, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France

    A. Siegfried

  6. Service de Neurochirurgie, Hôpital de la Cavale Blanche, CHRU de Brest, Université de Brest, Brest, France

    R. Seizeur

  7. Service d’Anatomie et Cytologie Pathologiques, CRB BB-0033-00035, CHRU de Nancy, INSERM U1256, Université de Lorraine, 54500, Vandœuvre-lès-Nancy, France

    G. Gauchotte

  8. U1035 Inserm - Biothérapie des Maladies Génétiques, Inflammatoires et Cancers (BMGIC), Univ. Bordeaux, 33076, Bordeaux, France

    D. Cappellen

  9. Service de Biologie des Tumeurs, CHU de Bordeaux - Hôpital du Haut Lévêque, 33604, Pessac, France

    D. Cappellen

  10. AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Epiniere, ICM, 75013, Paris, France

    C. Carpentier

  11. Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, CHU Timone, Service d’Anatomie Pathologique et de Neuropathologie, Marseille, France

    D. Figarella-Branger

  12. Service de Pathologie, CHU de Bordeaux, Hôpital Pellegrin, 33076, Bordeaux, France

    S. Eimer

  13. Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR 5286, Cancer Cell Plasticity department, Université Claude Bernard Lyon 1, Lyon, France

    D. Meyronet & F. Ducray

  14. Neuro-oncology Department, Hospices Civils de Lyon, Lyon, France

    D. Meyronet & F. Ducray

Authors
  1. L. Poetsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Bronnimann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Loiseau
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. S. Frénel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Siegfried
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Seizeur
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Gauchotte
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. Cappellen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. Carpentier
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D. Figarella-Branger
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S. Eimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. D. Meyronet
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. F. Ducray
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

POLA network

  • C. Desenclos
  • , H Sevestre
  • , P Menei
  • , A Rousseau
  • , T Cruel
  • , S Lopez
  • , M-I Mihai
  • , A Petit
  • , C. Adam
  • , F Parker
  • , R Seizeur
  • , I Quintin-Roué
  • , S Eimer
  • , H Loiseau
  • , L Bekaert
  • , F Chapon
  • , D Ricard
  • , C. Godfraind
  • , T Khallil
  • , D Cazals-Hatem
  • , T Faillot
  • , C. Gaultier
  • , MC. Tortel
  • , I Carpiuc
  • , P Richard
  • , W Lahiani
  • , H Aubriot-Lorton
  • , F Ghiringhelli
  • , E Le Rhun
  • , CA. Maurage
  • , EM Gueye
  • , F Labrousse
  • , F Ducray
  • , D Meyronnet
  • , D Figarella-Branger
  • , O Chinot
  • , L Bauchet
  • , V Rigau
  • , P Beauchesne
  • , G Gauchotte
  • , M Campone
  • , D Loussouarn
  • , D Fontaine
  • , F Vandenbos-Burel
  • , C. Blechet
  • , M Fesneau
  • , A Carpentier
  • , C. Dehais
  • , JY Delattre
  • , K Mokhtari
  • , M Polivka
  • , S Milin
  • , M Wager
  • , P Colin
  • , MD Diebold
  • , D Chiforeanu
  • , E Vauleon
  • , O Langlois
  • , A Laquerriere
  • , F Forest
  • , MJ Motso-Fotso
  • , M Andraud
  • , G Runavot
  • , B Lhermitte
  • , G Noel
  • , AL Di Stéfano
  • , C. Villa
  • , C. Rousselot-Denis
  • , I Zemmoura
  • , N Desse
  • , E Cohen-Moyal
  • , E Uro-Coste
  •  & F Dhermain

Corresponding author

Correspondence to C. Bronnimann.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The members of the French POLA network was in included in the Acknowledgements section.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Electronic supplementary material 1 (DOCX 32 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Poetsch, L., Bronnimann, C., Loiseau, H. et al. Characteristics of IDH-mutant gliomas with non-canonical IDH mutation. J Neurooncol 151, 279–286 (2021). https://doi.org/10.1007/s11060-020-03662-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-020-03662-x

Keywords

  • Non-canonical IDH mutant gliomas
  • Inherited predisposition to cancer
  • Infra-tentorial gliomas
  • Multicentric gliomas