Cell Reports (Sep 2023)
Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma
- David Gentien,
- Elnaz Saberi-Ansari,
- Nicolas Servant,
- Ariane Jolly,
- Pierre de la Grange,
- Fariba Némati,
- Géraldine Liot,
- Simon Saule,
- Aurélie Teissandier,
- Deborah Bourc’his,
- Elodie Girard,
- Jennifer Wong,
- Julien Masliah-Planchon,
- Erkan Narmanli,
- Yuanlong Liu,
- Emma Torun,
- Rebecca Goulancourt,
- Manuel Rodrigues,
- Laure Villoing Gaudé,
- Cécile Reyes,
- Matéo Bazire,
- Thomas Chenegros,
- Emilie Henry,
- Audrey Rapinat,
- Mylene Bohec,
- Sylvain Baulande,
- Radhia M’kacher,
- Eric Jeandidier,
- André Nicolas,
- Giovanni Ciriello,
- Raphael Margueron,
- Didier Decaudin,
- Nathalie Cassoux,
- Sophie Piperno-Neumann,
- Marc-Henri Stern,
- Johan Harmen Gibcus,
- Job Dekker,
- Edith Heard,
- Sergio Roman-Roman,
- Joshua J. Waterfall
Affiliations
- David Gentien
- 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; Corresponding author
- Elnaz Saberi-Ansari
- 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
- Nicolas Servant
- INSERM U900, Mines ParisTech, 75248 Paris, France
- Ariane Jolly
- GenoSplice, Paris, France
- Pierre de la Grange
- GenoSplice, Paris, France
- Fariba Némati
- 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
- Géraldine Liot
- Institut Curie, PSL Research University, CNRS, INSERM, UMR3347, U1021, Orsay, France
- Simon Saule
- 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
- Aurélie Teissandier
- Institut Curie, PSL Research University, Sorbonne University, INSERM U934, CNRS UMR 3215, 75005 Paris, France
- Deborah Bourc’his
- Institut Curie, PSL Research University, Sorbonne University, INSERM U934, CNRS UMR 3215, 75005 Paris, France
- Elodie Girard
- INSERM U900, Mines ParisTech, 75248 Paris, France
- Jennifer Wong
- Department of Diagnostic and Theranostic Molecular Pathology, Unit of Somatic Genetic, Hospital, Institut Curie, Paris, France
- Julien Masliah-Planchon
- Department of Diagnostic and Theranostic Molecular Pathology, Unit of Somatic Genetic, Hospital, Institut Curie, Paris, France
- Erkan Narmanli
- 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
- Yuanlong Liu
- Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Cancer Center Leman, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland
- Emma Torun
- Institut Curie, PSL Research University, Sorbonne University, INSERM U934, CNRS UMR 3215, 75005 Paris, France
- Rebecca Goulancourt
- GenoSplice, Paris, France
- Manuel Rodrigues
- 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
- Laure Villoing Gaudé
- 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
- Cécile Reyes
- 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
- Matéo Bazire
- 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
- Thomas Chenegros
- 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
- Emilie Henry
- 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
- Audrey Rapinat
- 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
- Mylene Bohec
- Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, PSL Research University, Paris, France
- Sylvain Baulande
- Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, PSL Research University, Paris, France
- Radhia M’kacher
- Cell Environment, DNA Damage R&D, 75020 Paris, France
- Eric Jeandidier
- Laboratoire de Génétique, Groupe Hospitalier de la Région de Mulhouse Sud-Alsace, Mulhouse, France
- André Nicolas
- Pathex, Institut Curie, PSL Research University, Paris, France
- Giovanni Ciriello
- Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Cancer Center Leman, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland
- Raphael Margueron
- Institut Curie, PSL Research University, Sorbonne University, INSERM U934, CNRS UMR 3215, 75005 Paris, France
- Didier Decaudin
- 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
- Nathalie Cassoux
- 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
- Sophie Piperno-Neumann
- Department of Medical Oncology, Institut Curie, PSL Research University, 75005 Paris, France
- Marc-Henri Stern
- 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
- Johan Harmen Gibcus
- Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA
- Job Dekker
- Howard Hughes Medical Institute, Department of Systems Biology, Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA
- Edith Heard
- Director’s Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
- Sergio Roman-Roman
- Translational Research Department, Research Center, Institut Curie, Paris Sciences et Lettres (PSL) Research University, 75005 Paris, France; Corresponding author
- Joshua J. Waterfall
- 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; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 9
p. 113132
Abstract
Summary: 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.
