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Study links genetic mutations to development of uveal melanoma and blue nevi
N Engl J Med. 2010;363(23):2191-2199.
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Novel genetic mutations were identified in a significant majority of uveal melanoma samples, offering vital new insight into the pathogenesis of the world's most common intraocular cancer, a study found.
Genetic mutations associated with uveal melanoma were previously unknown. There are no known treatments for metastatic uveal melanoma.
Researchers found GNA11, an oncogene, present in more than 40% of tumor samples taken from patients with uveal melanoma. They had previously linked GNAQ, another oncogene, to the highly metastatic neoplasm.
"Constitutive activation of the pathway involving these two genes appears to be a major contributor to the development of uveal melanoma," the authors said. "Our findings suggest that a large majority of uveal melanomas and blue nevi carry mutations in either GNAQ or GNA11."
Investigators extracted DNA from tumor samples of human subjects, performed genetic sequencing and injected engineered cells into immunocompromised mice to confirm the formation of tumors.
They sequenced all coding exons of GNAQ and GNA11 in a sample of 97 uveal melanomas and 45 blue nevi.
Between 63.2% and 74.5% of blue nevi, and 83% of primary uveal melanomas, had mutations in GNAQ or GNA11. Mutations at the codon R183 were less common than mutations at the codon Q209 in either oncogene.
Mutations in GNA11 spurred metastatic tumor formation in the mouse model.