Aggressive uveal melanoma: new mechanisms revealed

Institut Curie is a leading center worldwide for treating patients with uveal melanoma, a rare form of eye cancer with around 400 cases each year in France*. At the Research Center, several teams are working on the molecular and cellular mechanisms that promote the development of these tumors and their spread, or produce a therapeutic response.

These teams include those at the CurieCoreTech Genomics Platform headed by Dr. David Gentien, the Integrative Functional Genomics of Cancer team (Inserm U830) led by Dr. Joshua Waterfall and the Translational Research Department headed by Dr. Sergio Roman Roman. Researchers studied the genetic signs and epigenetic markers of the aggressive forms of these tumors.

First of all, they revealed a recurring characteristic of aggressive uveal melanoma, namely their genomic instability, including both aberrations in the number of copies and structural rearrangements.

They then looked at the gene suppressing the BAP1 tumor, which is normally responsible for preventing the formation of cancerous clusters. They found that the deactivation of this gene was a result not of mutations in the coding regions, but of the suppression of certain parts of the DNA that control its activity.

The final aspect of the study looked at the PRAME gene, often very active in aggressive uveal melanoma. The researchers revealed an activator of this gene that is responsible for its over-expression. Further studies must now be done to explain the entire mechanism at play and to counter resistance to immunotherapy.

These results offer a great many options for the development of new therapeutic approaches

Reference: D. Gentien et al.
Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma, Cell Reports (2023)

*National estimates of the incidence and mortality rate of cancer in metropolitan France between 1990 and 2018. Volume 1 – Solid tumors. Saint-Maurice (Fra): Santé publique France, 2019. 372 p.