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Prognostic impact of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in malignant gliomas†
Article first published online: 26 NOV 2012
Copyright © 2012 American Cancer Society
Volume 119, Issue 4, pages 806–813, 15 February 2013
How to Cite
Wang, X.-W., Boisselier, B., Rossetto, M., Marie, Y., Idbaih, A., Mokhtari, K., Gousias, K., Hoang-Xuan, K., Delattre, J.-Y., Simon, M., Labussière, M. and Sanson, M. (2013), Prognostic impact of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in malignant gliomas. Cancer, 119: 806–813. doi: 10.1002/cncr.27798
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.
- Issue published online: 4 FEB 2013
- Article first published online: 26 NOV 2012
- Manuscript Accepted: 30 JUL 2012
- Manuscript Revised: 13 JUL 2012
- Manuscript Received: 2 JUN 2012
- prognostic markers;
- single-nucleotide polymorphism
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.
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.
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.
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.