IDH1 mutations in grade II astrocytomas are associated with unfavorable progression‐free survival and prolonged postrecurrence survival
Open Access
- 29 June 2011
- Vol. 118 (2), 452-460
- https://doi.org/10.1002/cncr.26298
Abstract
BACKGROUND: The favorable prognostic impact of mutations in the IDH1 gene is well documented for malignant gliomas; its influence on World Health Organization (WHO) grade II astrocytomas, however, is still under debate. METHODS: A previously published database of 127 predominantly surgically treated patients harboring WHO grade II astrocytomas was revisited. Patients were screened for TP53 mutations (sequencing analysis), IDH1 mutations (pyrosequencing), and MGMT promoter methylation (methylation‐specific polymerase chain reaction and bisulfite sequencing). Endpoints were overall survival, progression‐free survival (PFS), time to malignant transformation, and postrecurrence survival. Radiotherapy was usually withheld until tumor progression/malignant transformation occurred. RESULTS: IDH1 mutations, TP53 mutations, and methylated MGMT promoters were seen in 78.1%, 51.2%, and 80.0% of the analyzed tumors, respectively. IDH1 mutations, which were significantly associated with TP53 mutations and/or MGMT promoter methylation (P < .001), resulted in shortened PFS (median, 47 vs 84 months; P = .004); postrecurrence survival, however, was significantly increased in those patients undergoing malignant transformation (median, 49 vs 13.5 months; P = .006). Overall survival was not affected by IDH1. A similar pattern of influence was seen for MGMT promoter methylation. Methylated tumors did significantly worse (better) in terms of PFS (postrecurrence survival); a low number of unmethylated tumors, however, limited the power of this analysis. Conversely, TP53 mutations were stringently associated with a worse prognosis throughout the course of the disease. CONCLUSIONS: IDH1 mutations are associated with a Janus headlike phenomenon; unfavorable prognostic influence on PFS turns into favorable impact on postrecurrence survival. A similar pattern of influence might exist for MGMT methylation. Cancer 2011;. © 2011 American Cancer Society.Keywords
This publication has 31 references indexed in Scilit:
- DNA Methylation, Isocitrate Dehydrogenase Mutation, and Survival in GliomaJNCI Journal of the National Cancer Institute, 2011
- Molecular Classification of Low-Grade Diffuse GliomasThe American Journal of Pathology, 2010
- Methylation profiling identifies 2 groups of gliomas according to their tumorigenesisNeuro-Oncology, 2010
- Cancer-associated IDH1 mutations produce 2-hydroxyglutarateNature, 2009
- IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomasNeuro-Oncology, 2009
- IDH1 Mutations Are Early Events in the Development of Astrocytomas and OligodendrogliomasThe American Journal of Pathology, 2009
- Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1αScience, 2009
- IDH1andIDH2Mutations in GliomasNew England Journal of Medicine, 2009
- An Integrated Genomic Analysis of Human Glioblastoma MultiformeScience, 2008
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958