Gene identified for spread of deadly melanoma

Researchers at Washington University School of Medicine in St. Louis have identified a gene linked to the spread of eye melanoma.

Although more research is needed, the researchers say the discovery is an important step in understanding why some tumors spread (metastasize) and others don’t. They believe the findings could lead to more effective treatments.

Reporting online in the journal Science Express, the team found mutations in a gene called BAP1 in 84 percent of the metastatic eye tumors they studied. In contrast, the mutation was rare in tumors that did not metastasize.

Metastasis is the most common cause of death in cancer patients, yet little is known about how cancer cells evolve the ability to spread to other parts of the body. There is growing evidence that mutations in so-called metastasis suppressor genes may promote the spread of cancer, while having little to do with earlier stages in the life of a tumor. Very few such genes have been identified, but this finding strongly implicates BAP1 as a new member of that small group.

“Scientists and physicians have been waiting for a rational, therapeutic target that we could use to treat high-risk patients,” says first author and Washington University ophthalmologist J. William Harbour, MD. “We believe this discovery may provide insights needed to hasten the development of therapies for these patients.”

A cancerous melanoma tumor (dark area, upper right) is seen below the retina.

Harbour laboratory

Ocular melanoma, also called uveal melanoma, is the most common eye cancer and the second-most common form of melanoma, striking about 2,000 adults in the United States each year. It can affect people at any age but is most common in patients over 50. The tumors arise from pigment cells, called melanocytes, that reside in the layer below the retina called the uveal tract. Up to half of those with the cancer eventually develop metastatic disease, which is universally fatal.

“The most common site where the cancer spreads is the liver,” Harbour says. “If it spreads, it goes to the liver about 90 percent of the time, generally leading to death within months.”

To improve survival, scientists need to understand more about what causes the tumor cells to metastasize, according to Harbour, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences, professor of cell biology and of molecular oncology and director of ocular oncology at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

Harbour and co-investigator Anne M. Bowcock, PhD, professor of genetics of pediatrics and of medicine, have been looking at DNA in tumor cells for clues about why some tumors spread. Tumors had already been grouped into two classes based on gene expression profiles. Class 1 tumors have a low risk of spreading, while class 2 tumors carry a high risk of metastasis. In addition, 90 percent of class 2 tumors have lost a copy of chromosome 3, unlike class 1 tumors, which tend to retain both copies of the chromosome.