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. 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.

PubMed ID: 23918605

Projects: GGN - German Glioma Network

Publication type: Not specified

Journal: Clin Cancer Res

Human Diseases: Glioblastoma multiforme

Citation: Clin Cancer Res. 2013 Sep 15;19(18):5146-57. doi: 10.1158/1078-0432.CCR-13-0017. Epub 2013 Aug 5.

Date Published: 15th Sep 2013

Registered Mode: by PubMed ID

Authors: C. Hartmann, B. Hentschel, M. Simon, M. Westphal, G. Schackert, J. C. Tonn, M. Loeffler, G. Reifenberger, T. Pietsch, A. von Deimling, M. Weller

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Created: 6th May 2019 at 12:57

Last updated: 7th Dec 2021 at 17:58

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