The ocular oncology laboratory has made great strides in understanding uveal melanoma, the most common primary cancer of the eye. The lab found that primary uveal melanomas can be divided based on gene expression profile into class 1 (low metastatic risk) and class 2 (high metastatic risk). The metastasizing class 2 tumors show a loss of melanocyte differentiation and reversion to a primitive stem-like phenotype. The lab developed a clinical prognostic test based on a 15-gene signature that has been validated in multiple studies, including a prospective multicenter study. This test is now being used for routine clinical testing at the vast majority of ocular oncology centers in the Unites States, Canada, Australia and several other countries.

 

Using Next Generation sequencing techniques, the ocular oncology lab then discovered that inactivating mutations in the tumor suppressor gene BAP1 are responsible for metastasis of class 2 tumors. Further work in the lab showed that a class of therapeutic compounds called histone deacetylase inhibitors can reverse the biochemical effects of BAP1 loss and may play a role in the clinical care of cancer patients. Clinical trials are in the planning stages to test this hypothesis.

Discovery of mutations in BAP1 by the ocular oncology lab has led to the discovery of the BAP1 familial cancer syndrome, which is transmitted in an autosomal dominant fashion and can include uveal and cutaneous melanoma, atypical cutaneous nevi, mesothelioma, meningioma, lung and breast cancer, and several other cancers. A clinical genetic test is being developed for screening high risk families.

The two major research directions in the lab are: (1) continue to use genomic techniques to identify new genetic alterations associated tumor initiation and progression in major forms of eye cancer, and (2) use cell-based and experimental models to understand the biological significance of these genetic alterations.