학술논문
Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma
Document Type
article
Author
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
Source
Cell Reports, Vol 42, Iss 9, Pp 113132- (2023)
Subject
Language
English
ISSN
2211-1247
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.