Details

Autor(en) / Beteiligte

• Houillier, C
• Wang, X
• Kaloshi, G
• Mokhtari, K
• Guillevin, R
• Laffaire, J
• Paris, S
• Boisselier, B
• Idbaih, A
• Laigle-Donadey, F
• Hoang-Xuan, K
• Sanson, M
• Delattre, J-Y

Titel

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

Ist Teil von

• Neurology, 2010-10, Vol.75 (17), p.1560-1566

Ort / Verlag

United States

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.