We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using formalin-fixed, paraffin-embedded material and correlate the results with clinicopathological parameters.
Although the role of guanine nucleotide-binding protein subunit α (GNA) 11 (GNA11) in melanoma has been described, the involvement of GNA14 in endometrial carcinoma remains to be determined.
Recent genomic studies have shown that mutations within components of G protein-coupled receptor (GPCR) signaling are early events associated with approximately 98% of uveal melanomas.<b>Implications:</b> This review discusses the alterations in GPCR signaling components (GNAQ and GNA11), dysregulated GPCR signaling cascades, and viable targeted therapies with the intent to provide insight into new therapeutic strategies in uveal melanoma.<i></i>.
Twenty primary LMNs ranging from benign and intermediate-grade melanocytomas to melanomas were tested by direct sequencing for hotspot mutations in the genes GNA11, GNAQ, BRAF, NRAS and HRAS.
These G-alpha protein mutations occur in the genes GNAQ and GNA11 and are seen at a high frequency in uveal melanomas, those melanomas that begin in the eye.
To examine whether GNAQ and GNA11 somatic mutations previously identified in uveal melanomas of Caucasians are associated with uveal melanomas in Chinese patients.
However, somatic mutations in either GNAQ or GNA11 are unique to UM tumors and could be used as potential markers to differentiate UM from metastatic CM and act as direct therapeutic targets.
Deep sequencing studies show that 4.2% of tumours carry activating mutations in GNAS (encoding Gαs), and that oncogenic activating mutations in genes encoding Gαq family members (GNAQ or GNA11) are present in ~66% and ~6% of melanomas arising in the eye and skin, respectively.
Only 1 out of 92 (1.1%) melanomas showed a mutation in GNA11 exon 4 codon 183, whereas 39 out of 92 (42.4%) harboured a mutation in exon 5 of GNA11 codon 209.
The mutations, such as those in NRAS, BRAF, GNAQ and GNA11, promote the growth of melanoma cells in most part through the mitogen-activated protein kinase (MAPK) pathway.
Primary CNS melanocytic neoplasms, including uveal melanomas have frequent mutations in GNAQ and GNA11, but are rare in cutaneous and mucosal melanomas.
Recently, mutually exclusive oncogenic mutations in melanomas involving NRAS (15-20%), BRAF (50%), CKIT (2%), and GNAQ/GNA11 (50% of uveal melanomas) have been identified.