000134863 001__ 134863 000134863 005__ 20240229105045.0 000134863 0247_ $$2doi$$a10.1093/neuonc/nox216 000134863 0247_ $$2pmid$$apmid:29165638 000134863 0247_ $$2pmc$$apmc:PMC5961072 000134863 0247_ $$2ISSN$$a1522-8517 000134863 0247_ $$2ISSN$$a1523-5866 000134863 0247_ $$2altmetric$$aaltmetric:29096945 000134863 037__ $$aDKFZ-2018-00653 000134863 041__ $$aeng 000134863 082__ $$a610 000134863 1001_ $$0P:(DE-He78)c0538fae462bd98e3cd8d54ed885b0eb$$aPfaff, Elke$$b0$$eFirst author 000134863 245__ $$aFeasibility of real-time molecular profiling for patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation-the NCT Neuro Master Match (N2M2) pilot study. 000134863 260__ $$aOxford$$bOxford Univ. Press$$c2018 000134863 3367_ $$2DRIVER$$aarticle 000134863 3367_ $$2DataCite$$aOutput Types/Journal article 000134863 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1660116200_9237 000134863 3367_ $$2BibTeX$$aARTICLE 000134863 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000134863 3367_ $$00$$2EndNote$$aJournal Article 000134863 500__ $$aPfaff E*, Kessler T* (*first author") / David T. W. Jones,# Wolfgang Wick,# and Felix Sahm# last authors 000134863 520__ $$aO6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a predictive biomarker in glioblastoma patients. Glioblastoma without hypermethylated MGMT promoter is largely resistant to treatment with temozolomide. These patients are in particular need of new treatment approaches, which are offered by biomarker-driven clinical trials with targeted drugs based on molecular characterization of individual tumors.In preparation for an upcoming clinical study, a comprehensive molecular profiling approach was undertaken on tissues from 43 glioblastoma patients harboring an unmethylated MGMT promoter at diagnosis. The diagnostic pipeline covered various levels of molecular characteristics, including whole-exome sequencing, low-coverage whole-genome sequencing, RNA sequencing, as well as microarray-based gene expression profiling and DNA methylation arrays.Complex multilayer molecular diagnostics were feasible in this setting with a median turnaround time of 4-5 weeks from surgery to the molecular tumor board. In 35% of cases, potentially relevant therapeutic decisions were derived from the data. Alterations were most frequently found in receptor tyrosine kinases, members of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin and mitogen-activated protein kinase pathway as well as cell cycle control and p53 regulation cascades. Individual tumors harbored clonal alterations such as oncogenic fusions of tyrosine kinases which constitute promising targets for targeted therapies. A prioritization algorithm is proposed to allocate patients with multiple targets to the potentially best treatment option.With this feasibility study, a comprehensive molecular profiling approach for patients with newly diagnosed glioblastoma harboring an unmethylated MGMT promoter is presented. Analyses in this pilot cohort serve as a basis for trials based on targetable alterations and on the question of allocation of patients to the best treatment arm. 000134863 536__ $$0G:(DE-HGF)POF3-317$$a317 - Translational cancer research (POF3-317)$$cPOF3-317$$fPOF III$$x0 000134863 588__ $$aDataset connected to CrossRef, PubMed, 000134863 7001_ $$0P:(DE-He78)5c2c9cbe6ce72553684d82d94aebdadd$$aKessler, Tobias$$b1$$eFirst author 000134863 7001_ $$0P:(DE-HGF)0$$aBalasubramanian, Gnana Prakash$$b2 000134863 7001_ $$0P:(DE-HGF)0$$aBerberich, Anne$$b3 000134863 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b4 000134863 7001_ $$0P:(DE-HGF)0$$aWick, Antje$$b5 000134863 7001_ $$0P:(DE-He78)8714da4e45acfa36ce87c291443a9218$$aDebus, Jürgen$$b6 000134863 7001_ $$aUnterberg, Andreas$$b7 000134863 7001_ $$aBendszus, Martin$$b8 000134863 7001_ $$aHerold-Mende, Christel$$b9 000134863 7001_ $$aCapper, David$$b10 000134863 7001_ $$0P:(DE-HGF)0$$aSchenkel, Irini$$b11 000134863 7001_ $$0P:(DE-He78)cef2261a4b41e6c8b36045623e0a025d$$aEisenmenger, Andreas$$b12 000134863 7001_ $$0P:(DE-He78)8b508b91c472089d47f0930c895fd342$$aDettmer, Susan$$b13 000134863 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b14 000134863 7001_ $$0P:(DE-He78)5ef8651b0f857b9c640aa5b1498c43b5$$aPlatten, Michael$$b15 000134863 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b16 000134863 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b17 000134863 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b18$$eLast author 000134863 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b19$$eLast author 000134863 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b20$$eLast author 000134863 773__ $$0PERI:(DE-600)2094060-9$$a10.1093/neuonc/nox216$$gVol. 20, no. 6, p. 826 - 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