GNA11 (G Protein Subunit Alpha 11)

KDR encodes vascular endothelial growth factor (VEGF) receptor 2, a central regulator of endothelial proliferation and angiogenesis. This previously unreported variant in CH implicates receptor tyrosine kinase-mediated VEGF signaling as a distinct pathogenic mechanism and expands the molecular spectrum of CH, suggesting a biologically distinct subset of tumors lacking canonical GNA11/GNAQ mutations.

The presence of MS appeared to correlate with worse clinical outcomes, as 67% of patients with MS died, compared to none without. Our findings expand the recognized molecular diversity of MBNs and provide insights into their biological behaviors, underscoring the clinical significance of identifying potential prognostic factors.

Using an unbiased approach, we identify Src-family kinase member LYN, and guanine nucleotide-binding protein G(i) alpha subunit proteins, GNAI1, GNAI2, and GNAI3 as novel binding partners of MSLN in AML and show that pharmacological or genetic inhibition of LYN signaling restores NOMO-1 cell sensitivity to Ara-C. Together, these findings demonstrate that MSLN functions as an oncogenic driver in AML and reveal a previously unrecognized MSLN-LYN signaling axis, the therapeutic targeting of which may enhance responses to chemotherapy.

P2, N=4, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

A genetic evaluation identified a pathogenic GNA11 variant (c.178C > T, p.Arg60Cys), consistent with autosomal dominant hypocalcemia type 2 (ADH2). This case expands the understanding of ADH2 and raises important questions about optimal treatment strategies in patients with coexisting genetic and postsurgical hypoparathyroidism.

This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management.

SETD2 deletion potentiates isochromosome formation across diverse cancers. Combinatorial targeting of MITF together with a previously identified synthetic lethal gene may benefit UVM patients harboring both chr3 deletion and 8q+.

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.