Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.

Autor:	Bredel M; Department 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., Espinosa L; Cancer Research Program, Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Institut Mar d'Investigacions Mèdiques, Hospital del Mar, 08003 Barcelona, Spain., Kim H; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Scholtens DM; Division of Biostatistics-Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., McElroy JP; Center for Biostatistics-Department of Biomedical Informatics, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA., Rajbhandari R; Department of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA., Meng W; Department of Radiation Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA., Kollmeyer TM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA., Malta TM; Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI 48202, USA., Quezada MA; Department of Neurology & Neurological Sciences and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Harsh GR; Department of Neurological Surgery, University of California at Davis School of Medicine, Sacramento, CA 95817, USA., Lobo-Jarne T; Cancer Research Program, Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Institut Mar d'Investigacions Mèdiques, Hospital del Mar, 08003 Barcelona, Spain., Solé L; Cancer Research Program, Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Institut Mar d'Investigacions Mèdiques, Hospital del Mar, 08003 Barcelona, Spain., Merati A; Department of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA., Nagaraja S; Department of Neurology & Neurological Sciences and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Nair S; Department of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA., White JJ; Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC 27103, USA., Thudi NK; Department of Radiation Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA., Fleming JL; Department of Radiation Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA., Webb A; Center for Biostatistics-Department of Biomedical Informatics, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA., Natsume A; Department of Neurosurgery, Nagoya University School of Medicine, Nagoya 464-8601, Japan., Ogawa S; Department of Pathology and Tumor Biology, Kyoto University, Kyoto 606-8501, Japan., Weber RG; Institute for Human Genetics, Hannover Medical School, 30625 Hannover, Germany., Bertran J; Biosciences Department, Faculty of Sciences, Technology, and Engineering. University of Vic-Central University of Catalonia, 08500 Vic, Spain., Haque SJ; Department of Radiation Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA., Hentschel B; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany., Miller CR; Division of Neuropathology-Department of Pathology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35294, USA., Furnari FB; Laboratory of Tumor Biology, Division of Regenerative Medicine-Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA., Chan TA; Center for Immunotherapy and Precision Immuno-Oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Grosu AL; Department of Radiation Oncology, Comprehensive Cancer Center, University of Freiburg, 79106 Freiburg, Germany., Weller M; Department of Neurology, University Hospital and University of Zurich, 8091 Zurich, Switzerland., Barnholtz-Sloan JS; Division of Cancer Epidemiology and Genetics-National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Monje M; Department of Neurology & Neurological Sciences and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Noushmehr H; Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI 48202, USA., Jenkins RB; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA., Rogers CL; Gamma West Cancer Services, Salt Lake City, UT 84124, USA., MacDonald DR; London Regional Cancer Program, Western University, London, ON N6A 5W9, Canada., Pugh SL; NRG Oncology Statistics and Data Management Center, Philadelphia, PA 19103, USA., Chakravarti A; Department of Radiation Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2023 Jun 20; Vol. 4 (6), pp. 101082.
DOI:	10.1016/j.xcrm.2023.101082
Abstrakt:	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. Competing Interests: Declaration of interests M.B.: NIH/NINDS grant R01NS117641, advisory board membership and grant (Varian Medical Systems), consulting (MRIMath). L.E.: Instituto de Salud Carlos III grant PI22/00069. T.L.-J.: an Asociación Española Contra el Cáncer grant. G.R.H.: NIH/NIBIB grant (P41-EB032840-01). J.S.B.-S.: NIH/NCI grants to Case Western Reserve University School of Medicine. J.P.M.: MOU between OSU Radiation Oncology and OSU Center for Biostatistics. R.B.J.: NIH grants. A.W.: MOU between OSU Radiation Oncology and OSU Biomedical Informatics. T.A.C.: grants (PGDX, Pfizer, AstraZeneca, Illumina, NysnoBio); royalties (PGDX); consulting (Illumina, NysnoBio, Pfizer, BMS, Merck, LG Chem); patents (TMB as predictor of immunotherapy response); stock (Griststone Bio, Nysno Bio). A.N.: consulting (Daiichi-Sankyo, NGK, SparkPlug) to his institution; $2,000 as honoraria. M.W.: grants (Apogenix, Merck, Sharp & Dohme, Merck [EMD], Philogen, Quercis); consulting (Adastra, Medac, Merck [EMD], Nerviano Medical Sciences, Novartis); honoraria (Bristol Meyer Squibb, Medac, Merck, Sharp & Dohme); Data Safety Monitoring Board or Advisory Board (Orbus and Philogen); leadership (EORTC). R.G.W.: grant 70-3163-Wi 3 (German Cancer Aid). S.O.: grant (Cordia Therapeutics, Dainippon-Sumitomo, Pharmaceuticals, Otsuka Assay Inc.); royalties (ASAHI Genomics, Qiagen); consulting (Cordia Therapeutics, Kan Research Institute, Novartis Pharmaceuticals); honoraria (MSD Japan, Kyowa Hakko Kirin, Pfizer); stocks (ASAHI Genomics, Cordia Therapeutics, Rebirthell). M.M.: NIH grants (R01NS092597, DP1NS111132, P50CA165962), grants from Kleberg Foundation Cancer Research, Ludwig Fund for Cancer Research; consulting (Cygnal Therapeutics); honoraria for lectures. C.R.M. and F.B.F.: NIH grant (R01CA258248). F.B.F.: NIH grant (R01NS080939). D.R.M.: clinical trials support (INTELLANCE-1 study [M13-813], CCTG CE.8 [EORTC-1709-BTG], INDIGO study [AG-881], Abbvie, Celgene, Agios [now Servier]). (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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