Glioblastomas with IDH1/2 mutations have a short clinical history and have a favorable clinical outcome

• Published in: Japanese journal of clinical oncology 2016-01, Vol.46 (1), p.31-39
• Main Authors: Ohno, Makoto, Narita, Yoshitaka, Miyakita, Yasuji, Matsushita, Yuko, Arita, Hideyuki, Yonezawa, Motoki, Yoshida, Akihiko, Fukushima, Shintaro, Takami, Hirokazu, Ichimura, Koichi, Shibui, Soichiro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Brain Neoplasms - enzymology; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Chemoradiotherapy; Chromosome Deletion; Chromosomes, Human, Pair 1 - genetics; Dacarbazine - administration & dosage; Dacarbazine - analogs & derivatives; DNA Methylation; Female; Glioblastoma - enzymology; Glioblastoma - genetics; Glioblastoma - pathology; Guanine - analogs & derivatives; Guanine - metabolism; Humans; Isocitrate Dehydrogenase - genetics; Japan; Kaplan-Meier Estimate; Karnofsky Performance Status; Male; Middle Aged; Mutation; Predictive Value of Tests; Prognosis; Promoter Regions, Genetic
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyv170

Glioblastomas with isocitrate dehydrogenase 1/2 mutations comprise a biologically distinct subgroup of glioblastomas. We studied isocitrate dehydrogenase 1/2 mutant glioblastomas at the clinical, molecular and radiological levels to define their clinical features, including the prognostic value of isocitrate dehydrogenase 1/2 mutations compared with isocitrate dehydrogenase 1/2 wild-type glioblastomas. We investigated 128 newly diagnosed glioblastoma patients who were treated at our institute between January 2005 and May 2013. Isocitrate dehydrogenase 1/2 mutation status was determined using pyrosequencing. O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation and 1p/19q co-deletions were also analyzed using pyrosequencing and multiplex ligation-dependent probe amplification, respectively. Isocitrate dehydrogenase 1/2 mutations were detected in 10 of 128 patients (7.8%). Isocitrate dehydrogenase 1/2 mutations were correlated with a younger age, the presence of an oligodendroglial component and 1p/19q co-deletions and a longer survival time. The interval from initial symptom to initial operation did not differ according to isocitrate dehydrogenase 1/2 mutation status (median interval: 2.3 versus 1.2 months; P = 0.13). Two of three isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions had an oligodendroglial component and were associated with a prolonged survival time. Multivariate analysis of 90 patients treated with temozolomide-based chemoradiotherapy indicated that age, extent of resection, postoperative Karnofsky performance score and O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation were correlated with better survival. Isocitrate dehydrogenase 1/2 mutations showed a trend for improved survival (P = 0.068). Most isocitrate dehydrogenase 1/2 mutant glioblastomas have a short clinical history, and some isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions behave like oligodendroglial tumors. Isocitrate dehydrogenase 1/2 mutations may have a positive prognostic impact on the Japanese population.