Acta Neuropathologica

, Volume 120, Issue 6, pp 719–729

Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis

  • Philippe Metellus
  • Bema Coulibaly
  • Carole Colin
  • Andre Maues de Paula
  • Alexandre Vasiljevic
  • David Taieb
  • Anne Barlier
  • Blandine Boisselier
  • Karima Mokhtari
  • Xiao Wei Wang
  • Anderson Loundou
  • Frederique Chapon
  • Sandrine Pineau
  • L’Houcine Ouafik
  • Olivier Chinot
  • Dominique Figarella-Branger
Original Paper

DOI: 10.1007/s00401-010-0777-8

Cite this article as:
Metellus, P., Coulibaly, B., Colin, C. et al. Acta Neuropathol (2010) 120: 719. doi:10.1007/s00401-010-0777-8

Abstract

The phenotypic heterogeneity of low-grade gliomas (LGGs) is still inconsistently explained by known molecular abnormalities in patients treated according to the present standards of care. IDH1 codon 132 and IDH2 codon 172 sequencing was performed in a series of 47 LGGs and correlated with clinical presentation, MR imaging characteristics, genomic profile and outcome. A total of 38 IDH1 mutations at codon 132 and 2 IDH2 mutations at codon 172 were found, including 35 R132H (87.5%), 2 R132C (5.0%), 1 R132S (2.5%) and 2 R172 M (5%). The IDH mutations were significantly associated with 1p19q deleted genotype (P = 0.031) and p53 expression (P = 0.014). The presence (vs. absence) of IDH mutations was associated with a better outcome (5-year survival rate, 93% vs. 51%, respectively, P = 0.000001). After adjustment for age, tumor location and size, radiologic infiltration pattern and extent of surgery, multivariate analysis confirmed that IDH mutations was an independent favorable prognostic factor (hazard ratio = 40.9; 95% CI, 2.89–578.49, P = 0.006). Furthermore, we showed that patients with IDH-nonmutated tumors were significantly older (P = 0.020) and that these tumors involved significantly more frequently the insula (P = 0.004), were larger in size (>6 cm, P = 0.047), displayed an infiltrative pattern on MRI (P = 0.007) and were all p53 negative with no 1p19q deletion (P < 10−6). The absence of IDH mutations in LGGs identifies a novel entity of LGGs with distinctive location, infiltrative behavior, specific molecular alterations, and dismal outcome. These findings could significantly modify the LGG classification and may represent a new tool to guide patient-tailored therapy.

Keywords

Isocitrate dehydrogenase-1(IDH1) IDH2 Low-grade glioma p53 LOH 1p19q mutation Prognosis 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Philippe Metellus
    • 1
    • 2
    • 3
    • 13
  • Bema Coulibaly
    • 4
  • Carole Colin
    • 2
    • 3
  • Andre Maues de Paula
    • 4
  • Alexandre Vasiljevic
    • 4
  • David Taieb
    • 5
  • Anne Barlier
    • 6
    • 3
  • Blandine Boisselier
    • 7
    • 8
    • 9
  • Karima Mokhtari
    • 7
    • 8
    • 9
  • Xiao Wei Wang
    • 7
    • 8
    • 9
  • Anderson Loundou
    • 10
  • Frederique Chapon
    • 11
  • Sandrine Pineau
    • 11
  • L’Houcine Ouafik
    • 2
    • 3
  • Olivier Chinot
    • 2
    • 3
    • 12
  • Dominique Figarella-Branger
    • 2
    • 3
    • 4
  1. 1.Service de NeurochirurgieAssistance Publique-Hôpitaux de Marseille, Hôpital de la TimoneMarseilleFrance
  2. 2.INSERM, UMR 911MarseilleFrance
  3. 3.Faculté de MédecineAix-Marseille UniversitéMarseilleFrance
  4. 4.Service d’Anatomie Pathologique et de NeuropathologieAssistance Publique-Hôpitaux de Marseille, Hôpital de la TimoneMarseilleFrance
  5. 5.Service Central de Biophysique et Médecine nucléaireAssistance Publique-Hôpitaux de Marseille, Hôpital de la TimoneMarseilleFrance
  6. 6.CNRS, UMR 6544MarseilleFrance
  7. 7.Université Pierre et Marie Curie, Paris 6, CRICM, UMR-S975ParisFrance
  8. 8.INSERM, U 975ParisFrance
  9. 9.CNRS, UMR 7225ParisFrance
  10. 10.Assistance Publique-Hôpitaux de Marseille, Hôpital de la Timone, Unité d’Aide méthodologique à la Recherche Clinique et Epidémiologique, DRRCMarseilleFrance
  11. 11.Service de NeuroradiologieAssistance Publique-Hôpitaux de Marseille, Hôpital de la TimoneMarseilleFrance
  12. 12.Assistance Publique-Hôpitaux de Marseille, Hôpital de la Timone, Unité de NeurooncologieMarseilleFrance
  13. 13.Service de NeurochirurgieHôpital de la TimoneMarseille CedexFrance

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