دورية أكاديمية
أعرض في EDS

Integrated longitudinal analysis of adult grade 4 diffuse gliomas with long-term relapse interval revealed upregulation of TGF-β signaling in recurrent tumors.

التفاصيل البيبلوغرافية
العنوان: Integrated longitudinal analysis of adult grade 4 diffuse gliomas with long-term relapse interval revealed upregulation of TGF-β signaling in recurrent tumors.
المؤلفون: Kashani E; Institute of Pathology, University of Bern, Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland., Schnidrig D; Department for BioMedical Research, University of Bern, Bern, Switzerland.; SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland., Gheinani AH; Urological Diseases Research Center, Boston Children's Hospital, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Ninck MS; Institute of Pathology, University of Bern, Bern, Switzerland., Zens P; Institute of Pathology, University of Bern, Bern, Switzerland.; Graduate School for Health Sciences, University of Bern, Bern, Switzerland., Maragkou T; Institute of Pathology, University of Bern, Bern, Switzerland., Baumgartner U; Cell and Molecular Biology Department, QIMR Berghofer Medical Research Institute, Sid Faithfull Brain Cancer Laboratory, Brisbane, Australia.; School of Biomedical Sciences, University of Queensland, Brisbane, Australia., Schucht P; Department of Neurosurgery, University Hospital Bern, Bern, Switzerland., Rätsch G; SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.; ETH Zurich, Zurich, Switzerland., Rubin MA; Department for BioMedical Research, University of Bern, Bern, Switzerland.; Bern Center for Precision Medicine, Bern, Switzerland., Berezowska S; Institute of Pathology, University of Bern, Bern, Switzerland.; Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Ng CKY; Department for BioMedical Research, University of Bern, Bern, Switzerland.; SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.; Bern Center for Precision Medicine, Bern, Switzerland., Vassella E; Institute of Pathology, University of Bern, Bern, Switzerland.
مؤلفون مشاركون: SOCIBP consortium
المصدر: Neuro-oncology [Neuro Oncol] 2023 Apr 06; Vol. 25 (4), pp. 662-673.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2010- : Oxford : Oxford University Press
Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub.,
مواضيع طبية MeSH: Glioma*/pathology , MicroRNAs*/genetics , Brain Neoplasms*/metabolism, Humans ; Adult ; Up-Regulation ; Epithelial-Mesenchymal Transition/genetics ; Retrospective Studies ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/metabolism ; Recurrence ; RNA, Messenger/metabolism ; Cell Line, Tumor ; Activin Receptors, Type I/genetics ; Activin Receptors, Type I/metabolism
مستخلص: Background: Adult-type diffuse gliomas, CNS WHO grade 4 are the most aggressive primary brain tumors and represent a particular challenge for therapeutic intervention.
Methods: In a single-center retrospective study of matched pairs of initial and post-therapeutic glioma cases with a recurrence period greater than 1 year, we performed whole exome sequencing combined with mRNA and microRNA expression profiling to identify processes that are altered in recurrent gliomas.
Results: Mutational analysis of recurrent gliomas revealed early branching evolution in 75% of the patients. High plasticity was confirmed at the mRNA and miRNA levels. SBS1 signature was reduced and SBS11 was elevated, demonstrating the effect of alkylating agent therapy on the mutational landscape. There was no evidence for secondary genomic alterations driving therapy resistance. ALK7/ACVR1C and LTBP1 were upregulated, whereas LEFTY2 was downregulated, pointing towards enhanced Tumor Growth Factor β (TGF-β) signaling in recurrent gliomas. Consistently, altered microRNA expression profiles pointed towards enhanced Nuclear Factor Kappa B and Wnt signaling that, cooperatively with TGF-β, induces epithelial to mesenchymal transition (EMT), migration, and stemness. TGF-β-induced expression of pro-apoptotic proteins and repression of antiapoptotic proteins were uncoupled in the recurrent tumor.
Conclusions: Our results suggest an important role of TGF-β signaling in recurrent gliomas. This may have clinical implications since TGF-β inhibitors have entered clinical phase studies and may potentially be used in combination therapy to interfere with chemoradiation resistance. Recurrent gliomas show high incidence of early branching evolution. High tumor plasticity is confirmed at the level of microRNA and mRNA expression profiles.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
التعليقات: Erratum in: Neuro Oncol. 2023 Feb 14;25(2):430. (PMID: 36524994)
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فهرسة مساهمة: Investigator: A Benjak; R Bruggmann; F Comoglio; A Kahles; I Keller; C K Y Ng; S Piscuoglio; L Prélot; G Rätsch; M A Rubin; D Schnidrig; S Selimovic-Hamza; TM Thomas
Keywords: Glioblastoma; TGF-β signaling; longitudinal analysis; miRNA; tumor evolution
المشرفين على المادة: 0 (Transforming Growth Factor beta)
0 (MicroRNAs)
0 (RNA, Messenger)
EC 2.7.11.30 (ACVR1C protein, human)
EC 2.7.11.30 (Activin Receptors, Type I)
تواريخ الأحداث: Date Created: 20220920 Date Completed: 20230407 Latest Revision: 20230413
رمز التحديث: 20230414
مُعرف محوري في PubMed: PMC10076939
DOI: 10.1093/neuonc/noac220
PMID: 36124685
قاعدة البيانات: MEDLINE
الوصف
تدمد:1523-5866
DOI:10.1093/neuonc/noac220