GNA11 (G Protein Subunit Alpha 11)

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 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.

This report demonstrates that fully automated cfDNA-based NGS can achieve clinically meaningful genomic profiling within 27 h in a community hospital. This advancement addresses the time and cost barriers of traditional NGS analysis and represents a significant step toward promoting precision medicine in community healthcare.

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 cohort, K-RAS and GNAS mutational analysis in cyst fluid did not improve the detection of mucinous pancreatic cysts significantly after conventional testing. However, the method may be useful due to its high specificity in uncertain cases.

The patient remains tumor-free at 20-month follow-up. This case highlights the rare malignant transformation of craniofacial fibrous dysplasia, demonstrates the importance of molecular analysis for confirmation of its etiogenesis, and illustrates the challenges associated with reconstruction of the orbit and maxilla following cancer resection.

In the randomized SCANDIUM II trial, patients with metastatic UM received a one-time treatment with isolated hepatic perfusion using high-dose melphalan in combination with systemic immune checkpoint inhibition with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Patients with undetectable ctDNA 2-4 months after the start of treatment had significantly improved progression-free survival (P = 0.024), and a non-significant improvement in overall survival. In patients with UM liver metastases treated with combined hepatic perfusion and immune checkpoint inhibition, ctDNA may serve as a predictive biomarker and warrants further validation.

The detection of GNAQ/GNA11 mutations in ctDNA at baseline was associated with an inferior outcome. (ClinicalTrials.gov: NCT01377025).

Clinically, our findings highlight the importance of differentiating EDM from common blue spots, and we recommend ophthalmological investigation even in the absence of periocular cutaneous involvement. The association with CNS infarct is unclear, but we suggest clinical neurological features be sought and MRI undertaken if there are concerns. Genetically, these results not only expand the causative genotype of EDM, but also challenge our concept of the Mosaic Disorders currently described with HRAS, ACTB, PIK3CA, and GNA11. Stratification by genotype may help determine patient melanoma risk more accurately in the future. Patient- and variant-specific genetic counselling should be given where there is a potential risk of germline transmission to offspring.