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Prognostic impact of the isocitrate dehydrogenase 1 single‐nucleotide polymorphism rs11554137 in malignant gliomas
Author(s) -
Wang XiaoWei,
Boisselier Blandine,
Rossetto Marta,
Marie Yannick,
Idbaih Ahmed,
Mokhtari Karima,
Gousias Konstantinos,
HoangXuan Khê,
Delattre JeanYves,
Simon Matthias,
Labussière Marianne,
Sanson Marc
Publication year - 2012
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.27798
Subject(s) - isocitrate dehydrogenase , idh1 , medicine , idh2 , glioma , single nucleotide polymorphism , myeloid leukemia , snp , oncology , gastroenterology , genotype , cohort , mutation , cancer research , genetics , biology , gene , biochemistry , enzyme
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 ( IDH1 105GGT ) was identified in 98 of 952 patients (10.3%) and was not associated with the codon 132 ( IDH1 132 ) mutation. Patients who had GMB with the IDH1 105GGT 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 IDH1 105GGT 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.