Author Interviews, Biomarkers, JAMA, Melanoma, Ophthalmology / 30.04.2016
MedicalResearch.com Interview with:
J. William Harbour, M.D.
Leader, Eye Cancer Site Disease Group
Sylvester Comprehensive Cancer Center University of Miami Miller School of MedicineMedicalResearch.com: What is the background for this study? What are the main findings? Dr. Harbour: Uveal melanoma (UM) is the most common primary cancer of the eye which has the fatal tendency to metastasis to the liver. The molecular landscape of UMs have been well characterized and can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low risk) and Class 2 (high risk). The Class 2 profile is strongly associated with mutations in the tumor suppressor BAP1. This GEP-based test is the only prognostic test for UM to undergo a prospective multicenter validation, an it is available commercially as DecisionDX-UM (Castle Biosciences, Inc). It is routinely used in many North American centers. The identification of driver mutations in cancer has become a focus of precision medicine for prognostic and therapeutic decision making in oncology. In UM, thus far, only 5 genes have been reported to be commonly mutated: BAP1, GNA11, GNAQ, EIF1AX, and SF3B1. In this study, we analyzed the associations between these 5 mutations, and with GEP classification, clinicopathologic features, and patient outcomes. The study showed that GNAQ and GNA11 are mutually exclusive, probably occur early in tumor formation, and are not associated with prognosis. In contrast, BAP1, SF3B1, and EIF1AX, which are also nearly mutually exclusive, likely occur later in tumor formation and do have prognostic value in UM. (more…)