Uveal Melanoma

This real-world study analyzed the genomic landscape of GNAQ and GNA11 mutations in 5,416 patients with metastatic solid tumors. It revealed that these mutations, while known in uveal melanoma, are also present in other cancers such as colorectal, melanoma, and gastric cancer. An immunogenic subgroup, characterized by non-hotspot mutations and high TMB or MSI, was identified and associated with potential benefit from immune checkpoint inhibitors. Canonical hotspot mutations, conversely, were predominant in TMB-low/MSS tumors. These findings highlight the importance of differentiating driver mutations from bystander mutations to guide therapeutic strategies.

This retrospective study utilized targeted next-generation sequencing to identify genetic variants with prognostic value in uveal melanoma. Mutations in BAP1, CHEK2, and DICER1 were independently associated with a poorer prognosis and increased metastatic risk. Furthermore, BAP1 and LRP1B mutations were linked to epithelioid/mixed histology, while SF3B1 mutation was associated with spindle cell morphology. These findings suggest that mutational profiling could improve risk stratification and patient follow-up.