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Qi S.-T.,Southern Medical University | Yu L.,Southern Medical University | Lu Y.-T.,Southern Medical University | Ou Y.-H.,Southern Medical University | And 3 more authors.
Oncology Reports | Year: 2011

Mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) appear to occur frequently and selectively in gliomas. Our aim was to assess whether IDH mutations are common in Chinese glioma patients and whether the mutations predict good response to concomitant chemoradiotherapy. In this study IDH1 and IDH2 mutations were detected in a series of 203 gliomas. IDH1 mutations were present in 75 of the 203 cases (36.9%) while IDH2 mutations in 5 of the 203 cases (2.5%). No tumor was mutated in both IDH1 and IDH2. IDH1/2 mutations were associated with prolonged overall survival in the whole series of patients exclusive of pilocytic astrocytoma (P<0.001), WHO grade II patients who received no adjuvant therapy after surgery (P=0.014) and WHO grade III patients who received concomitant chemoradiotherapy (standard schedule) after surgery (P=0.033). Furthermore, there was no correlation between IDH1/2 mutations and reponse to concomitant chemoradiotherapy in anaplastic gliomas. Our results suggest that IDH1 mutations also occur freuqently in Chinese glioma patients but the frequency of IDH1 mutations is below the findings reported by North American and European groups. Furthermore, we confirm the prognostic significance of IDH1/2 mutations in gliomas, but the mutations cannot predict a favorable response to concomitant chemoradiotherapy in anaplastic gliomas.


Songtao Q.,Southern Medical University | Lei Y.,Southern Medical University | Si G.,Guangzhou Medical College | Yanqing D.,Southern Medical University | And 4 more authors.
Cancer Science | Year: 2012

Recent studies have shown that isocitrate dehydrogenase1/2 (IDH1/2) mutations occur frequently in secondary glioblastoma. This study aimed to investigate their impact on temozolomide chemosensitivity and relationship with O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation in secondary glioblastoma. Searches for IDH1 and IDH2 mutations, 1p19q codeletion, MGMT promoter methylation, and p53 expression were carried out in a series of 86 secondary glioblastomas and correlated with progression-free survival and overall survival. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, then correlated with molecular alterations. IDH (IDH1 or IDH2) mutations were found in 58/79 patients (73.4%). IDH mutation, MGMT promoter methylation, and 1p19q codeletion were associated with prolonged progression-free survival in univariate (P<0.001, P<0.001, P=0.003, respectively) and multivariate analysis (P<0.001, P<0.001, P=0.035, respectively). IDH mutation (P=0.001) and MGMT promoter methylation (P=0.011) were correlated with a higher rate of objective response to temozolomide. Further analysis of response to temozolomide showed that patients with both IDH mutation and MGMT promoter methylation had the best response rate to temozolomide. IDH mutation appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. Use of IDH status combined with MGMT promoter status as a stratification factor seems appropriate in future clinical trials involving temozolomide for the treatment of patients with secondary glioblastoma. © 2011 Japanese Cancer Association.

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