Although uveal melanoma often results in fatal metastasis, scientists have now found a mutated gene that appears to predict a good outcome for this disease, the most common primary cancer of the eye.
J. William Harbour, MD, an eye surgeon at the University of Miami in Coral Gables, Florida, and Anne M. Bowcock, PhD, a genetics professor at Washington University School of Medicine in St. Louis, Missouri, led a team that found mutations in the SF3B1 gene.
“The good news is that these mutations develop in a distinct subtype of melanomas in the eye that are unlikely to spread and become deadly,” explained Bowcock in a statement issued by the Washington University School of Medicine to announce the group’s findings, which were published in Nature Genetics (2013;45:133-135).
According to the statement, uveal melanomas make up approximately 5% of all melanomas, occurring in an estimated 2,000 persons per year. Patients are often asymptomatic, but the tumor becomes fatal when it metastasizes to the liver.
In earlier work, Harbour and Bowcock identified a commonly mutated gene, BAP1, in persons with uveal melanoma. They found BAP1 alterations in about 80% of uveal melanomas with a poor prognosis. In the current research, the investigators sequenced uveal melanoma DNA from seven patients with no BAP1 mutations and from 11 patients with such mutations. Alterations in SF3B1 were discovered in three of these patients, and eventually in nearly 20% of 102 additional uveal tumors. According to Bowcock, this is the first time mutations in this gene have been found in uveal melanoma.
The presence of SF3B1 mutations was associated with favorable features including a younger age at diagnosis and a far lower metastasis rate than normally seen in uveal melanoma.
Presence of BAP1 mutations and presence of SF3B1mutations were found to be almost mutually exclusive of one another, suggesting that mutations in these genes may represent alternative pathways in tumor progression.