Prognostic Value of IDH1 Mutations Identified with PCR-RFLP Assay in Glioblastoma Patients
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Mol Diagn Ther 2010; 14 (3): 163-169 1177-1062/10/0003-0163/$49.95/0
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Prognostic Value of IDH1 Mutations Identified with PCR-RFLP Assay in Glioblastoma Patients Mateusz Bujko,1 Paulina Kober,1 Ewa Matyja,2 Pawe! Nauman,3 Katarzyna Dyttus-Cebulok,4 Beata Czeremszyn´ska,5 Wies!aw Bonicki 3 and Janusz A. Siedlecki1 1 2 3 4 5
Department of Molecular Biology, Maria Sk"odowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Department of Experimental and Clinical Neuropathology, M. Mossakowski Medical Research Center, Warsaw, Poland Department of Neurooncology, Maria Sk"odowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Department of Radiotherapy, Maria Sk"odowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Department of Radiotherapy, Ministry of Internal Affairs and Administration Hospital and Warmia and Mazury Oncology Centre, Olsztyn, Poland
Abstract
Background and Objective: It has been shown that somatic missense mutations in codon 132 of the NADP+ dependent isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors including highly malignant glioblastoma (GBM). The aim of this study was to evaluate a PCR-restriction fragment length polymorphism (RFLP)-based method for missense mutation detection and to estimate the prognostic value of the two most frequent IDH1 codon 132 mutations, R132H and R132C, in patients with newly diagnosed GBM treated with radiation combined with temozolomide. Methods: DNA was extracted from formalin-fixed, paraffin-embedded tissue. The PCR-RFLP method was adapted to IDH1 codon 132 mutation screening. The mutation status was determined in a group of 58 patients. Results: We found R132H mutations in 14% of patients. No R132C mutation was found in this study. Median follow-up for living patients was 31 (range 17–51) months. Median progression-free survival in the group of patients with IDH1 mutation was 29 months compared with 10 months in the IDH1 wild-type group (p = 0.004; hazard ratio [HR] 3.09, 95% CI 1.25, 4.78). Median overall survival in the group with IDH1 mutation has not been reached, whereas in the group with wild-type IDH1 it was 19.5 months (p < 0.001; HR 4.76, 95% CI 1.22, 6.30). Three-year overall survival was 60% in the group with IDH1 mutation while in the wild-type IDH1 group it dropped to 29%. IDH1 mutations significantly correlated with younger age (p = 0.02). Conclusions: Our results indicate that the IDH1 R132H mutation is a powerful prognostic marker in GBM treated with chemoradiation. The PCR-RFLP method allows for a fast, inexpensive, and sensitive mutation screening.
Introduction Glioblastoma (GBM), corresponding to WHO grade IV, is the most frequent primary brain tumor in adults. It represents 54% of all tumors originating from glial cells (Central Brain Tumor Registry of the United States, http://www. cbtrus.org), and is characterized by poor prognosis, with a median overall survival of 12 months.[1] Most GBM
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