Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations

• Verfasst von: Hartmann, Christian [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Titel: Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations
• Verf.angabe: 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
• E-Jahr: 2013
• Jahr: August 5, 2013
• Umfang: 13 S.
• Teil: volume:19
• Teil: year:2013
• Teil: number:18
• Teil: pages:5146-5157
• Teil: extent:13
• Fussnoten: Gesehen am 08.10.2021
• Titel Quelle: Enthalten in: Clinical cancer research
• Ort Quelle: Philadelphia, Pa. [u.a.] : AACR, 1995
• Jahr Quelle: 2013
• Band/Heft Quelle: 19(2013), 18, Seite 5146-5157
• ISSN Quelle: 1557-3265
• DOI: doi:10.1158/1078-0432.CCR-13-0017
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1749488787

Abstract

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.