There are many serious diseases that can affect the eyes. Ocular melanoma, also called uveal melanoma, is one of the more serious cancers that can occur in the eye. It is the most common eye cancer and the second most common form of melanoma in the human body, striking about 2,000 adults in the United States each year. It can affect people at any age, but is most common in patients older than 50. Up to half of patients with this cancer eventually develop metastatic disease (the cancer spreads to other parts of the body), which is universally fatal.
To improve survival, scientists need to understand more about what causes the tumor cells to spread. Recently, a study at Washington University School of Medicine in St. Louis identified a gene linked to the spread of eye melanoma. According to the study, mutations were found in the BAP1 gene in 84 percent of the metastatic eye tumors they studied. By contrast, the mutation was rare in tumors that did not metastasize. BAP1 is short for BRCA1 associated protein 1 and BRCA1 is linked to breast cancer in some women. The study, conducted by an ophthalmologist and a pediatric doctor, looked at the DNA in ocular melanoma tumor cells for clues.
Previously, scientists had grouped tumors into two classes based on their genetic profiles. Class I tumors have a low risk of spreading,while Class II tumors carry a high risk of spreading. In addition, they found 90 percent of Class II tumors have lost a copy of chromosome-3 unlike Class I tumors, which tend to retain both copies of chromosome-3. One of the scientists is quoted as saying, “We eliminated common genetic variations and then went back to look at which gene on chromosome-3 had additional alternations. There was one gene, BAP1, which had mutations in both of the initial Class II tumors that were analyzed. They went back and checked 29 more tumors of Class II and 25 tumors of Class I. They found 84 percent of the Class II tumors had damaging mutations in BAP1. They also found that in most cases of Class II tumor cells, there was only one chromosome-3.” It appears that what the gene is supposed to do is to act as a metastatic suppressor. When it is damaged, the tumor will spread.
There are several ways that this discovery could improve patient care. If we can detect BAP1 mutations at an earlier stage, we might be able to monitor a patient’s blood for detectable melanoma cells as an early sign that they are developing metastatic disease. It also would be useful to have a better understanding of the normal role of the BAP1 protein to provide insight into ways to therapeutically target eye tumors that are likely to spread. These studies are underway.
The BAP1 mutation represents only the second common genetic mutation ever reported in ocular melanoma, and it is the only mutation linked to metastasis of this type of cancer. This is good news not only for eye patients, but for dermatologic patients that also have forms of skin melanoma. The practice of medicine is rapidly changing, and we, in ophthalmology, are at the forefront in many areas of current, basic and clinical scientific research. Please don’t forget to get yearly eye exams and be sure to discuss with your ophthalmologist your family history of cancer and all the medications that you are using.
Dr. Kenneth Olander is an ophthalmologist for University Eye Surgeons.