IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group

作者：Martin J. van den Bent, Hendrikus Jan Dubbink, Yannick Marie, Alba Ariela Brandes, Martin Taphoorn, Pieter Wesseling, Marc Frénay, Cees C. Tijssen, Denis A. Lacombe, Ahmed Idbaïh, Ronald van Marion, Johan M. Kros, Winand N.M. Dinjens, Thierry Gorlia, Marc Sanson · 发表于：Clinical Cancer Research · 年份：2010 · DOI：10.1158/1078-0432.ccr-09-2902 · 被引用次数：381 · 研究领域：Glioma Diagnosis and Treatment、Brain Metastases and Treatment、Epigenetics and DNA Methylation

PURPOSE: Recent studies have shown the prognostic significance of IDH1 mutations in glioma. It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy. We determined the effect of IDH1 mutations on progression-free survival and overall survival (OS), and its correlation with other clinical and molecular features in the prospective randomized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine (PCV) in anaplastic oligodendroglioma. EXPERIMENTAL DESIGN: IDH1 and IDH2 alterations of the mutational hotspot codons R132 and R172 were assessed by the bidirectional cycle sequencing of PCR-amplified fragments. MGMT promoter methylation was assessed using methylation-specific multiplex ligation-dependant probe amplification based on methylation-sensitive restriction analysis. Loss of chromosomes 1p, 19q, 10, and 10q and the gain of 7 and the EGFR gene were assessed with fluorescence in situ hybridization. RESULTS: From 159 patients, sufficient material was available for IDH1 analysis. In 151 and 118 of these patients, respectively, the 1p/19q status and the MGMT promoter methylation status were known. In 73 cases (46%), an IDH1 mutation was found and only one IDH2 mutation was identified. The presence of IDH1 mutations correlated with 1p/19q codeletion and MGMT promoter methylation, and inversely correlated with loss of chromosome 10, EGFR amplification, polyso...