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Tytuł pozycji:

Long-term epilepsy-associated tumors: transcriptional signatures reflect clinical course.

Tytuł:
Long-term epilepsy-associated tumors: transcriptional signatures reflect clinical course.
Autorzy:
Delev D; Department of Neurosurgery, Medical Center, Freiburg, Germany. .; Department of Neurosurgery, RWTH University Aachen, Aachen, Germany. .; Translational NeuroOncology Research Group, Medical Center, University of Freiburg, Freiburg, Germany. .; Medical Faculty, Freiburg University, Freiburg, Germany. .
Daka K; Department of Neurosurgery, Medical Center, Freiburg, Germany.; Translational NeuroOncology Research Group, Medical Center, University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Heynckes S; Department of Neurosurgery, Medical Center, Freiburg, Germany.; Translational NeuroOncology Research Group, Medical Center, University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Gaebelein A; Department of Neurosurgery, Medical Center, Freiburg, Germany.; Translational NeuroOncology Research Group, Medical Center, University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Franco P; Department of Neurosurgery, Medical Center, Freiburg, Germany.; Translational NeuroOncology Research Group, Medical Center, University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Pfeifer D; Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Prinz M; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.; Center for NeuroModulation (NeuroModul), University of Freiburg, Freiburg, Germany.; Institute of Neuropathology, Medical Center, University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Schnell O; Department of Neurosurgery, Medical Center, Freiburg, Germany.; Translational NeuroOncology Research Group, Medical Center, University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Urbach H; Department of Neuroradiology, Medical Center, University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Mader I; Department of Neuroradiology, Medical Center, University of Freiburg, Freiburg, Germany.; Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik, Vogtareuth, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Beck J; Department of Neurosurgery, Medical Center, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Grote A; Clinic for Neurosurgery, Evangelic Hospital of Bethel, Bielefeld, Germany.
Becker AJ; Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
Heiland DH; Department of Neurosurgery, Medical Center, Freiburg, Germany.; Translational NeuroOncology Research Group, Medical Center, University of Freiburg, Freiburg, Germany.; Medical Faculty, Freiburg University, Freiburg, Germany.
Źródło:
Scientific reports [Sci Rep] 2020 Jan 09; Vol. 10 (1), pp. 96. Date of Electronic Publication: 2020 Jan 09.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural
Język:
English
Imprint Name(s):
Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:
Biomarkers, Tumor/*genetics
Brain Neoplasms/*etiology
Epilepsy/*complications
Neoplasm Recurrence, Local/*etiology
Adolescent ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Child ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Young Adult
References:
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Substance Nomenclature:
0 (Biomarkers, Tumor)
Entry Date(s):
Date Created: 20200111 Date Completed: 20201117 Latest Revision: 20210110
Update Code:
20240105
PubMed Central ID:
PMC6952384
DOI:
10.1038/s41598-019-56146-y
PMID:
31919458
Czasopismo naukowe
Long-term epilepsy-associated tumors (LEATs) represent mostly benign brain tumors associated with drug-resistant epilepsy. The aim of the study was to investigate the specific transcriptional signatures of those tumors and characterize their underlying oncogenic drivers. A cluster analysis of 65 transcriptome profiles from three independent datasets resulted in four distinct transcriptional subgroups. The first subgroup revealed transcriptional activation of STAT3 and TGF-signaling pathways and contained predominantly dysembryoplastic neuroepithelial tumors (DNTs). The second subgroup was characterized by alterations in the MAPK-pathway and up-stream cascades including FGFR and EGFR-mediated signaling. This tumor cluster exclusively contained neoplasms with somatic BRAF V600E mutations and abundance of gangliogliomas (GGs) with a significantly higher recurrence rate (42%). This finding was validated by examining recurrent tumors from the local database exhibiting BRAF V600E in 90% of the cases. The third cluster included younger patients with neuropathologically diagnosed GGs and abundance of the NOTCH- and mTOR-signaling pathways. The transcript signature of the fourth cluster (including both DNTs and GGs) was related to impaired neural function. Our analysis suggests distinct oncological pathomechanisms in long-term epilepsy-associated tumors. Transcriptional activation of MAPK-pathway and BRAF V600E mutation are associated with an increased risk for tumor recurrence and malignant progression, therefore the treatment of these tumors should integrate both epileptological and oncological aspects.
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