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

Fiche publication

Date publication

septembre 2023

Journal

Cell reports

Auteurs

Membres identifiés du Cancéropôle Est :
Dr JEANDIDIER Eric

Tous les auteurs :
Gentien D, Saberi-Ansari E, Servant N, Jolly A, de la Grange P, Némati F, Liot G, Saule S, Teissandier A, Bourc'his D, Girard E, Wong J, Masliah-Planchon J, Narmanli E, Liu Y, Torun E, Goulancourt R, Rodrigues M, Gaudé LV, Reyes C, Bazire M, Chenegros T, Henry E, Rapinat A, Bohec M, Baulande S, M'kacher R, Jeandidier E, Nicolas A, Ciriello G, Margueron R, Decaudin D, Cassoux N, Piperno-Neumann S, Stern MH, Gibcus JH, Dekker J, Heard E, Roman-Roman S, Waterfall JJ

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/37708024

Résumé

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.