GNAQ (G Protein Subunit Alpha Q)

Ex vivo dendritic cell-mediated T cell activation with vaccine constructs containing optimized structure produced cytolytic T cells that secreted IFN gamma and killed mutated GNAQ-expressing UM cells in vitro. These findings propose the utility of the fusion DNA vaccines in eliciting T cell immunity against UM cells bearing the Q209L mutation in GNAQ/GNA11 protein to prevent the establishment and progression of metastatic disease.

Trametinib monotherapy achieved a 39% DCR in patients lacking standard options, supporting further studies to confirm efficacy and identify predictive biomarkers for treatment response.

The tumor microenvironment featured immunosuppressive macrophage populations and exhausted T cells, closely resembling human UM. This physiologically relevant, immune-competent model provides a platform for investigating UM biology, functionally characterizing candidate driver genes, and developing immune-based therapeutic strategies.

The patient's recovery was stable, and she was discharged to rehabilitation on postoperative day 9. This case highlights the surgical nuances and diagnostic considerations involved in treating rare mixed intramedullary-extramedullary meningeal melanomas of the thoracic spine.

We further show that MITF, MYC, and GNAQ/GNA11 form coupled regulatory feedback loops in the melanocyte lineage, and MITF deletion in UVM creates acute dependency on MYC-mediated rescue via chr8q amplification, often as a consequence of isochromosome formation. The discovered feedback loops predict both overall and relapse-free patient survival within the most aggressive UVM subtype, explain sensitivity to therapeutic gene perturbations, and inform effective combinatorial therapies.

Therapies targeting specific genetic alterations and immunotherapy agents have been recently developed and introduced in clinical practice for the management of advanced-stage UMs. This review aims to present the latest advances in the clinical molecular pathology of UM, along with the resulting targeted, immunological, and other therapies that have been introduced or are currently under investigation.

Plasma analysis identified a pathogenic SPEN variant and human leukocyte antigen (HLA) genotype (HLA-A*02:17 and HLA-A*02:01 alleles), conferring therapeutic eligibility for tebentafusp, and molecular evidence supportive of metastatic uveal melanoma, enabling initiation of appropriate systemic therapy before additional tissue sampling...While the liquid biopsy and ablation of one of the lesions confirmed the diagnosis, the liquid biopsy was a key first step that provided a comprehensive diagnostic and prognostic picture without the need for an invasive procedure. This case highlights how integrating liquid biopsy into the diagnostic pathway for uveal melanoma can lead to earlier, more informed treatment decisions.

This analysis suggests that the variants in these genes can be confidently reported from RNA-Seq data obtained from an RNA-based fusion panel.

These findings support the adaptability of UVM lesions and suggest rational combination therapies targeting both primary GNAQ/GNA11-driven oncogenic signals and their compensatory networks as a more effective, personalized treatment approach for advanced UVM.

In this article, we review the major pathological entities observed in dermatopathology associated with GNAQ mutations and place them within this new understanding of ectomesenchyme. In doing so, we explain how a single gene can influence the development of various vascular and melanocytic pathologies, while also challenging the traditional relationship between melanocytes and endothelial cells and their common origin in the neural crest.

We describe a unique case of ovarian adenosarcoma presenting with bilateral ovarian involvement, manifesting at the more advanced stage IIIC, notably in the absence of sarcomatous overgrowth (SO). Moreover, we report for the first time the presence of LVI and the GNAQ missense variant in ovarian adenosarcoma.

Oral melanocytic neoplasms are rare and have distinct clinicopathological features. Despite this, a gap exists in molecular data regarding ODN and AMP. Conversely, OMN and OMM have distinct profiles; in particular, the latter may benefit modestly from tyrosine kinase inhibitor treatment, as KIT and BRAF mutations are sensitive to imatinib and vemurafenib, respectively.