Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma.

Autor:	Gentien D; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Genomics Platform, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France. Electronic address: dgentien@curie.fr., Saberi-Ansari E; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; INSERM U830, Research Center, Institut Curie, PSL Research University, 75005 Paris, France., Servant N; INSERM U900, Mines ParisTech, 75248 Paris, France., Jolly A; GenoSplice, Paris, France., de la Grange P; GenoSplice, Paris, France., Némati F; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL Research University, 75248 Paris, France., Liot G; Institut Curie, PSL Research University, CNRS, INSERM, UMR3347, U1021, Orsay, France., Saule S; Institut Curie, PSL Research University, CNRS, INSERM, UMR3347, U1021, Orsay, France; Université Paris-Saclay Centre National de La Recherche Scientifique, UMR 3347, Unité 1021, Orsay, France., Teissandier A; Institut Curie, PSL Research University, Sorbonne University, INSERM U934, CNRS UMR 3215, 75005 Paris, France., Bourc'his D; Institut Curie, PSL Research University, Sorbonne University, INSERM U934, CNRS UMR 3215, 75005 Paris, France., Girard E; INSERM U900, Mines ParisTech, 75248 Paris, France., Wong J; Department of Diagnostic and Theranostic Molecular Pathology, Unit of Somatic Genetic, Hospital, Institut Curie, Paris, France., Masliah-Planchon J; Department of Diagnostic and Theranostic Molecular Pathology, Unit of Somatic Genetic, Hospital, Institut Curie, Paris, France., Narmanli E; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; INSERM U830, Research Center, Institut Curie, PSL Research University, 75005 Paris, France., Liu Y; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Cancer Center Leman, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Torun E; Institut Curie, PSL Research University, Sorbonne University, INSERM U934, CNRS UMR 3215, 75005 Paris, France., Goulancourt R; GenoSplice, Paris, France., Rodrigues M; Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France; INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer, Department of Genetics, Institut Curie, PSL Research University, 75005 Paris, France., Gaudé LV; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Genomics Platform, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France., Reyes C; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Genomics Platform, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France., Bazire M; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Genomics Platform, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France., Chenegros T; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Genomics Platform, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France., Henry E; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Genomics Platform, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France., Rapinat A; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Genomics Platform, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France., Bohec M; Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, PSL Research University, Paris, France., Baulande S; Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, PSL Research University, Paris, France., M'kacher R; Cell Environment, DNA Damage R&D, 75020 Paris, France., Jeandidier E; Laboratoire de Génétique, Groupe Hospitalier de la Région de Mulhouse Sud-Alsace, Mulhouse, France., Nicolas A; Pathex, Institut Curie, PSL Research University, Paris, France., Ciriello G; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Cancer Center Leman, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Margueron R; Institut Curie, PSL Research University, Sorbonne University, INSERM U934, CNRS UMR 3215, 75005 Paris, France., Decaudin D; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL Research University, 75248 Paris, France., Cassoux N; Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France; Department of Ocular Oncology, Faculty of Medicine, Institut Curie, Université de Paris Descartes, 75005 Paris, France., Piperno-Neumann S; Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France., Stern MH; INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer, Department of Genetics, Institut Curie, PSL Research University, 75005 Paris, France., Gibcus JH; Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Dekker J; Howard Hughes Medical Institute, Department of Systems Biology, Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA., Heard E; Director's Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany., Roman-Roman S; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France. Electronic address: sergio.roman-roman@curie.fr., Waterfall JJ; Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; INSERM U830, Research Center, Institut Curie, PSL Research University, 75005 Paris, France. Electronic address: joshua.waterfall@curie.fr.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Sep 26; Vol. 42 (9), pp. 113132. Date of Electronic Publication: 2023 Sep 13.
DOI:	10.1016/j.celrep.2023.113132
Abstrakt:	Uveal melanoma (UM) is a rare cancer resulting from the transformation of melanocytes in the uveal tract. Integrative analysis has identified four molecular and clinical subsets of UM. To improve our molecular understanding of UM, we performed extensive multi-omics characterization comparing two aggressive UM patient-derived xenograft models with normal choroidal melanocytes, including DNA optical mapping, specific histone modifications, and DNA topology analysis using Hi-C. Our gene expression and cytogenetic analyses suggest that genomic instability is a hallmark of UM. We also identified a recurrent deletion in the BAP1 promoter resulting in loss of expression and associated with high risk of metastases in UM patients. Hi-C revealed chromatin topology changes associated with the upregulation of PRAME, an independent prognostic biomarker in UM, and a potential therapeutic target. Our findings illustrate how multi-omics approaches can improve our understanding of tumorigenesis and reveal two distinct mechanisms of gene expression dysregulation in UM. Competing Interests: Declaration of interests P.d.l.G. is a co-founder of Genosplice technology. A.J. and R.G. are employees of Genosplice technology. R.M. is the founder of Cell Environment. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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