Journal Article

DKFZ-2018-00653

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Feasibility of real-time molecular profiling for patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation-the NCT Neuro Master Match (N2M2) pilot study.

Pfaff, E. (First author)DKFZ* ; Kessler, T. (First author)DKFZ* ; Balasubramanian, G. P.DKFZ* ; Berberich, A.DKFZ* ; Schrimpf, D.DKFZ* ; Wick, A.DKFZ* ; Debus, J.DKFZ* ; Unterberg, A. ; Bendszus, M. ; Herold-Mende, C. ; Capper, D. ; Schenkel, I.DKFZ* ; Eisenmenger, A.DKFZ* ; Dettmer, S.DKFZ* ; Brors, B.DKFZ* ; Platten, M.DKFZ* ; Pfister, S.DKFZ* ; von Deimling, A.DKFZ* ; Jones, D. (Last author)DKFZ* ; Wick, W. (Last author)DKFZ* ; Sahm, F. (Last author)DKFZ*

2018
Oxford Univ. Press Oxford

This record in other databases:  

Please use a persistent id in citations: doi:10.1093/neuonc/nox216

Abstract: O6-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.

Note: Pfaff E*, Kessler T* (*first author") / David T. W. Jones,# Wolfgang Wick,# and Felix Sahm# last authors

---

Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK Heidelberg (L101)
3. KKE Neuroonkologie (G370)
4. Angewandte Bioinformatik (G200)
5. KKE Neuropathologie (G380)
6. E050 KKE Strahlentherapie (E050)
7. Klinische Studienzentrale (G040)
8. Neuroimmunologie und Hirntumorimmunologie (G160)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2018

---

Database coverage:
; Allianz-Lizenz / DFG ; Current Contents - Clinical Medicine ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---