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- Uveal Melanoma and the Lynch Syndrome Tumor Spectrum
Uveal Melanoma and the Lynch Syndrome Tumor Spectrum
Auteurs
Anaïs Le Ven, Marie-Charlotte Villy, André Bortolini Silveira, Alexandre Houy, Julien Masliah-Planchon, Mathilde Warcoin, Marine Le Mentec, Fatoumata Simaga, Antoine De Pauw, Bruno Buecher, Marion Gauthier-Villars, Thibault Verrier, Kevin Merchadou, Victor Renault, Anne Vincent-Salomon, Juliette Sauge, Sophie El Zein, Catherine Dubois d’Enghien, Sophie Piperno-Neumann, Alexandre Matet, Denis Malaise, Nathalie Cassoux, Livia Lumbroso-Le Rouic, Dominique Stoppa-Lyonnet, Marc-Henri Stern, Manuel Rodrigues, Lisa Golmard, Chrystelle Colas
Résumé
Importance
To date, no environmental factors and few therapeutic options are known for uveal melanoma (UM), the most common malignant intraocular primary tumor in adults. Identification of new predisposition factors could lead to better monitoring and possibly improved treatments of patients with UM.
Objective
To identify new genetic alterations predisposing for UM.
Design, Setting, and Participants
This was a prospective cohort study conducted at Institut Curie in Paris, France, among 381 consecutive patients diagnosed with UM between July 2021 and February 2023. UM was diagnosed clinically by ophthalmologists, and a senior pathologist confirmed the diagnosis when tumor or biopsy was available. All participants received genetic counseling and consented to extended genetic testing. A panel of 122 genes predisposing to cancer were analyzed by targeted sequencing on germline DNA from these patients.
Main Outcomes and Measures
Frequency of pathogenic variants (PVs) in genes from a targeted panel, with classification of germline PVs done according to the American College of Medical Genetics and Genomics guidelines and the French Unicancer Genetics Group.
Results
A total of 79 PVs were identified in 70 participants (41 female and 29 male; mean [SD] age, 60.6 [15.3] years). Among them, 21 were found in clinically relevant genes, with an enrichment in the mismatch repair (MMR) genes, involved in Lynch syndrome, a frequent predisposition to colon and endometrial cancers. This finding suggested MMR germline PVs could also predispose to UM. One tumor was available from a participant carrying a
Conclusions and Relevance
This prospective germline study on patients with UM provided evidence supporting the notion that MMR germline alterations are enriched among patients with UM and may contribute to oncogenesis of UM, and that UM may therefore be a rare tumor manifestation of Lynch syndrome.
