Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations
Purpose: The determinants of long-term survival in glioblastoma have remained largely obscure. Isocitrate dehydrogenase (IDH) 1 or 2 mutations are common in World Health Organization (WHO) grades II and III gliomas, but rare in primary glioblastomas, and associated with longer survival. - Experiment...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
August 5, 2013
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| In: |
Clinical cancer research
Year: 2013, Volume: 19, Issue: 18, Pages: 5146-5157 |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-13-0017 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-13-0017 Verlag, lizenzpflichtig, Volltext: https://clincancerres.aacrjournals.org/content/19/18/5146 
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| Author Notes: | Christian Hartmann, Bettina Hentschel, Matthias Simon, Manfred Westphal, Gabriele Schackert, Jörg C. Tonn, Markus Loeffler, Guido Reifenberger, Torsten Pietsch, Andreas von Deimling, Michael Weller, for the German Glioma Network |
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| 245 | 1 | 0 | |a Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations |c Christian Hartmann, Bettina Hentschel, Matthias Simon, Manfred Westphal, Gabriele Schackert, Jörg C. Tonn, Markus Loeffler, Guido Reifenberger, Torsten Pietsch, Andreas von Deimling, Michael Weller, for the German Glioma Network |
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| 520 | |a Purpose: The determinants of long-term survival in glioblastoma have remained largely obscure. Isocitrate dehydrogenase (IDH) 1 or 2 mutations are common in World Health Organization (WHO) grades II and III gliomas, but rare in primary glioblastomas, and associated with longer survival. - Experimental Design: We compared clinical and molecular characteristics of 69 patients with centrally confirmed glioblastoma and survival >36 months (LTS-36), including 33 patients surviving >60 months (LTS-60), with 257 patients surviving <36 months. MGMT promoter methylation, 1p/19q codeletions, EGFR amplification, TP53 mutations, and IDH1/2 mutations were determined by standard techniques. - Results: The rate of IDH1/2 mutations in LTS-36 patients was 34% (23 of 67 patients) as opposed to 4.3% in controls (11 of 257 patients). Long-term survivors with IDH1/2-mutant glioblastomas were younger, had almost no EGFR amplifications, but exhibited more often 1p/19q codeletions and TP53 mutations than LTS patients with IDH1/2 wild-type glioblastomas. Long-term survivors with IDH1/2 wild-type showed no distinguishing features from other patients with IDH1/2 wild-type glioblastomas except for a higher rate of MGMT promoter methylation. Similarly, among 11 patients with IDH1/2-mutant glioblastomas without long-term survival, the only difference to IDH1/2-mutant long-term survivors was less-frequent MGMT promoter methylation. Compared with LTS-36 patients, LTS-60 patients had less frequently TP53 mutations and radiotherapy alone as initial treatment. - Conclusions: IDH1/2 mutations define a subgroup of tumors of LTS patients that exhibit molecular characteristics of WHO grade II/III gliomas and secondary glioblastomas. Determinants of LTS with IDH1/2 wild-type glioblastomas, which exhibit typical molecular features of primary glioblastomas, beyond MGMT promoter methylation, remain to be identified. Clin Cancer Res; 19(18); 5146-57. ©2013 AACR. | ||
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