IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas

Oct 27, 2010Neurology

IDH1 or IDH2 gene mutations linked to longer survival and better response to temozolomide in low-grade brain tumors

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Abstract

IDH mutations are present in 70% of patients with low-grade gliomas.

IDH mutations and 1p-19q codeletion are linked to longer overall survival.
Both univariate and multivariate analyses support the association of IDH mutation and 1p-19q codeletion with improved survival outcomes.
1p-19q codeletion, MGMT promoter methylation, and IDH mutation are connected to a higher likelihood of response to temozolomide treatment.
In untreated low-grade gliomas, 1p-19q codeletion is associated with longer progression-free survival, while IDH mutation does not show a similar association.

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OBJECTIVES: Recent studies have shown that IDH1 and IDH2 mutations occur frequently in gliomas, including low-grade gliomas. However, their impact on the prognosis and chemosensitivity of low-grade gliomas remains unclear.

METHODS: Search for IDH1 and IDH2 mutations, loss of heterozygosity on chromosomes 1p and 19q, MGMT promoter methylation, and p53 expression was performed in a series of 271 low-grade gliomas and correlated with overall survival. A subgroup of 84 patients treated up-front with temozolomide was individualized. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, and then correlated with molecular alterations.

RESULTS: IDH (IDH1 or IDH2) mutations were found in 132/189 patients (70%). IDH mutation and 1p-19q codeletion were associated with prolonged overall survival in univariate (p = 0.002 and p = 0.0001) and multivariate analysis (p = 0.003 and p = 0.004). 1p-19q codeletion, MGMT promoter methylation, and IDH mutation (p = 0.01) were correlated with a higher rate of response to temozolomide. Further analysis of the course of the disease prior to any treatment except for surgery (untreated subgroup) showed that 1p-19q codeletion was associated with prolonged progression-free survival in univariate analysis, whereas IDH mutation was not.

CONCLUSION: IDH mutation appears to be a significant marker of positive prognosis and chemosensitivity in low-grade gliomas, independently of 1p-19q codeletion, whereas its impact on the course of untreated tumors seems to be limited.

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IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas

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