Prognostic impact of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in malignant gliomas

Authors

  • Xiao-Wei Wang MD,

    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
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  • Blandine Boisselier MSc,

    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
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  • Marta Rossetto MD,

    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
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  • Yannick Marie PhD,

    1. Genotyping and Sequencing Platform, ICM, Paris, France
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  • Ahmed Idbaih MD, PhD,

    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
    4. Department of Neurology, Pitie-Salpetriere Hospital, APHP, Paris, France
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  • Karima Mokhtari MD,

    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
    4. R. Escourolle Laboratory of Neuropathology, Pitie-Salpetriere Hospital, APHP, Paris, France
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  • Konstantinos Gousias MD,

    1. Department of Neurosurgery, University Clinic Bonn, Bonn, Germany
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  • Khê Hoang-Xuan MD, PhD,

    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
    4. Department of Neurology, Pitie-Salpetriere Hospital, APHP, Paris, France
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  • Jean-Yves Delattre MD,

    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
    4. Department of Neurology, Pitie-Salpetriere Hospital, APHP, Paris, France
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  • Matthias Simon MD,

    1. Department of Neurosurgery, University Clinic Bonn, Bonn, Germany
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  • Marianne Labussière PharmD, PhD,

    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
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  • Marc Sanson MD, PhD

    Corresponding author
    1. CRICM, Pierre and Marie Curie University, Paris, France
    2. INSERM U 975, Paris, France
    3. UMR 7225, CNRS, Paris, France
    4. Department of Neurology, Pitie-Salpetriere Hospital, APHP, Paris, France
    • Fédération de Neurologie Mazarin, Groupe Hospitalier Pitié-Salpêtrière, 75651, Paris Cedex 13, France

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    • Fax: (011) 33 1 42 16 03 75


  • We are indebted to the patients who agreed to participate in this study, to Anne-Marie Lekieffre and Muriel Brandel for their assistance with the study, and to the medical staff for collecting blood samples.

Abstract

BACKGROUND.

The IDH1 gene, which encodes isocitrate dehydrogenase 1, is frequently mutated in gliomas and acute myeloid leukemia. The single-nucleotide polymorphism (SNP) (reference SNP no. rs11554137:C>T) located on IDH1 codon 105 has been associated with a poor outcome in patients with acute myeloid leukemia but has not been investigated in patients with gliomas.

METHODS.

The IDH1 codon 105 SNP was genotyped first in a series of 952 patients with grade 2 through 4 gliomas and was correlated with outcomes and tumor genomic profile. Then, it was genotyped in 2 validations sets of 306 patients with glioblastoma (GBM) and 591 patients with glioma.

RESULTS.

The minor allele codon 105 glycine (GGT) SNP (IDH1105GGT) was identified in 98 of 952 patients (10.3%) and was not associated with the codon 132 (IDH1132) mutation. Patients who had GMB with the IDH1105GGT variant had a poorer outcome than patients without the variant (median overall survival [OS], 10.7 months vs 15.5 months; P = .001; median progression-free survival [PFS], 6.4 months vs 8.5 months; P = .003). The prognostic impact was confirmed in an independent validation set of 306 GBMs from the same center (median PFS, 6.8 months vs 9.7 months; P = .006; median OS, 13.9 months vs 18.8 months; P = .0187). In the second validation cohort (591 grade 2-4 gliomas), a significant association was observed between IDH1105GGT and an adverse prognosis for the overall series and for patients with World Health Organization grade 3 gliomas, but the difference did not reach significance in patients with GBM.

CONCLUSIONS.

Taken together, the current data strongly suggested an association between the SNP rs11554137:C>T polymorphism and adverse outcomes in patients with malignant glioma. A single-nucleotide polymorphism (SNP) located on codon 105 of the isocitrate dehydrogenase 1 (IDH1) gene (reference SNP rs11554137) is analyzed in 3 independent series of patients with gliomas. The SNP rs11554137 is independent of the occurrence of somatic mutation on IDH1 codon 132, but, per se, has a prognostic impact in malignant gliomas. Cancer 2013. © 2012 American Cancer Society.

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