Prognostic impact of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in malignant gliomas
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Published on: May 10, 2024
Xiao-Wei Wang1, Blandine Boisselier, Marta Rossetto
1CRICM, Pierre and Marie Curie University, Paris, France; INSERM U 975, Paris, France; UMR 7225, CNRS, Paris, France.
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.
