ArticleCell reports. Medicine2023
Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.
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Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5citing papers in PubMed
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5 citing papers in PubMed, 5 citations in OpenAlex.
- Identification of NF-κB pathway-related biomarkers in myocardial ischemia-reperfusion injury: based on transcriptomics analysis and RT-qPCR validation.Scientific reports · 2026Article
- NF-κB signaling as a critical inflammatory node in pulmonary arterial hypertension: from vascular remodeling to right heart failure.Frontiers in immunology · 2026Review
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Secondary exophytic glioblastoma of the cerebellopontine angle: a case report and review of the literature.Frontiers in oncology · 2025Article
- Effect of radiotherapy on head and neck cancer tissues in patients receiving radiotherapy: a bioinformatics analysis-based study.Scientific reports · 2024Article
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Authors and funding
39 authors at 20 institutions in 6 countries.
Markus BredelDepartment of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA. Electronic address: mbredel@uab.edu.
Lluís EspinosaCancer Research Program, Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Institut Mar d'Investigacions Mèdiques, Hospital del Mar, 08003 Barcelona, Spain.
Hyunsoo KimLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Denise M ScholtensDivision of Biostatistics-Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Joseph P McElroyCenter for Biostatistics-Department of Biomedical Informatics, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Rajani RajbhandariDepartment of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA.
Wei MengDepartment of Radiation Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Thomas M KollmeyerDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Tathiane M MaltaDepartment of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI 48202, USA.
Michael A QuezadaDepartment of Neurology & Neurological Sciences and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Griffith R HarshDepartment of Neurological Surgery, University of California at Davis School of Medicine, Sacramento, CA 95817, USA.
Teresa Lobo-JarneCancer Research Program, Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Institut Mar d'Investigacions Mèdiques, Hospital del Mar, 08003 Barcelona, Spain.
Laura SoléCancer Research Program, Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Institut Mar d'Investigacions Mèdiques, Hospital del Mar, 08003 Barcelona, Spain.
Aran MeratiDepartment of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA.
Surya NagarajaDepartment of Neurology & Neurological Sciences and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sindhu NairDepartment of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA.
Jaclyn J WhiteDepartment of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC 27103, USA.
Nanda K ThudiDepartment of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA.
Jessica L FlemingDepartment of Radiation Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Amy WebbCenter for Biostatistics-Department of Biomedical Informatics, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Atsushi NatsumeDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya 464-8601, Japan.
Seishi OgawaDepartment of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8501, Japan.
Ruthild G WeberInstitute for Human Genetics, Hannover Medical School, 30625 Hannover, Germany.
Joan BertranBiosciences Department, Faculty of Sciences, Technology, and Engineering. University of Vic-Central University of Catalonia, 08500 Vic, Spain.
S Jaharul HaqueDepartment of Radiation Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Bettina HentschelInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany.
C Ryan MillerDivision of Neuropathology-Department of Pathology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA.
Frank B FurnariLaboratory of Tumor Biology, Division of Regenerative Medicine-Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Timothy A ChanCenter for Immunotherapy and Precision Immuno-Oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Anca-Ligia GrosuDepartment of Radiation Oncology, Comprehensive Cancer Center, University of Freiburg, 79106 Freiburg, Germany.
Michael WellerDepartment of Neurology, University Hospital and University of Zurich, 8091 Zurich, Switzerland.
Jill S Barnholtz-SloanDivision of Cancer Epidemiology and Genetics-National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Michelle MonjeDepartment of Neurology & Neurological Sciences and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Houtan NoushmehrDepartment of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI 48202, USA.
Robert B JenkinsDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
C Leland RogersGamma West Cancer Services, Salt Lake City, UT 84124, USA.
David R MacDonaldLondon Regional Cancer Program, Western University, London, ON N6A 5W9, Canada.
Stephanie L PughNRG Oncology Statistics and Data Management Center, Philadelphia, PA 19103, USA.
Arnab ChakravartiDepartment of Radiation Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USUniversity of Alabama at Birmingham · USHoward Hughes Medical Institute · USCentro de Investigación Biomédica en Red de Cáncer · ESHenry Ford Health System · USMayo Clinic · USCancer Services · USCleveland Clinic Lerner College of Medicine · USKyoto University · JPLeipzig University · DEMedizinische Hochschule Hannover · DENagoya University Hospital · JPNational Cancer Institute · USNeurological Surgery · USNorthwestern University · USNRG Oncology · USUniversitat de Vic - Universitat Central de Catalunya · ESUniversity Medical Center Freiburg · DEUniversity of California San Diego · USUniversity of North Carolina at Chapel Hill · US
Funding
NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Lila J. Rutten · 1985 to 2026
$151.3MStatistics CoreU10CA180822 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI James J. Dignam · 2014 to 2026
$146.4MNRG Oncology NCORP Research Base-BIQSFPUG1CA189867 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI Deborah Watkins Bruner, Lisa A. Kachnic · 2014 to 2026
$140.5MNRG Oncology Biospecimen BankU24CA196067 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI Tanner J. Freeman, Nilsa Del Carmen Ramirez Milan · 2015 to 2026
$42.6MTargeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KEITH LLOYD LIGON · 2013 to 2026
$33.5MTOWARDS PRECISION IMMUNO-ONCOLOGY: UNRAVELING THE GENOMIC DETERMINANTS AND MECHANISMS UNDERLYING IMMUNOTHERAPY EFFICACY AND RESISTANCER35CA232097 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CHAN, TIMOTHY AN-THY · 2018 to 2024
$7.0MTRD3: Data Analytics and Intelligent Systems (AI-ML-DL-Visualization)P41EB032840 · NIBIB · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Griffith R. Harsh, Laura Marcu · 2022 to 2026
$6.7MGlioma Circuitry: Bridging Systems Neuroscience and CancerDP1NS111132 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2018 to 2022
$5.7MGenotypic Interactions in Brain Cancer HeterogeneityR01NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2012 to 2022
$3.5MCredentialing next-generation human glioma models for precision therapeuticsR01CA258248 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Frank Furnari, Christopher Ryan Miller · 2022 to 2026
$3.0MNeuronal activity-regulated mechanisms of glioma growthR01NS092597 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2016 to 2021
$2.1MNCI NIH HHS P30 CA015083NCI NIH HHS P50 CA165962NCI NIH HHS R01 CA258248NCI NIH HHS R35 CA232097NCI NIH HHS U10 CA180822NCI NIH HHS U10 CA180868NCI NIH HHS U24 CA196067NCI NIH HHS UG1 CA189867NIBIB NIH HHS P41 EB032840NINDS NIH HHS DP1 NS111132NINDS NIH HHS R01 NS080939NINDS NIH HHS R01 NS092597NINDS NIH HHS R01 NS117641
Abstract
Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas.
Indexed as
Brain NeoplasmsGliomaChildEpigenomeHaploinsufficiencyHumansIsocitrate DehydrogenaseMutationNF-KappaB Inhibitor alphaIsocitrate DehydrogenaseNF-KappaB Inhibitor alphaNFKBIA protein, humangliomaH3K27M mutationhaploinsufficiencyIDH mutationmethylomeNFKBIA deletionnomogramtumor suppressor
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