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Glioblastomas with IDH1/2 mutations have a short clinical history and have a favorable clinical outcome.
- Source :
-
Japanese journal of clinical oncology [Jpn J Clin Oncol] 2016 Jan; Vol. 46 (1), pp. 31-9. Date of Electronic Publication: 2015 Nov 24. - Publication Year :
- 2016
-
Abstract
- Objective: 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.<br />Methods: 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.<br />Results: 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).<br />Conclusions: 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.<br /> (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Brain Neoplasms enzymology
Brain Neoplasms pathology
Chemoradiotherapy
Chromosome Deletion
Chromosomes, Human, Pair 1 genetics
DNA Methylation
Dacarbazine administration & dosage
Dacarbazine analogs & derivatives
Female
Glioblastoma enzymology
Glioblastoma pathology
Guanine analogs & derivatives
Guanine metabolism
Humans
Japan
Kaplan-Meier Estimate
Karnofsky Performance Status
Male
Middle Aged
Predictive Value of Tests
Prognosis
Promoter Regions, Genetic
Temozolomide
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Brain Neoplasms genetics
Glioblastoma genetics
Isocitrate Dehydrogenase genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1465-3621
- Volume :
- 46
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Japanese journal of clinical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 26603354
- Full Text :
- https://doi.org/10.1093/jjco/hyv170