ST. LOUIS -- Finding a gene that triggers the spread of eye melanoma was a discovery whose time had come, said researcher Dr. J. William Harbour, professor of ophthalmology and visual sciences at Washington University School of Medicine.
The discovery demonstrates how science piggy-backs itself and leads to discoveries that wouldn't happen without other discoveries -- some of which are difficult to understand at the time they're discovered.
In this case, Washington University researchers discovered how a gene malfunctioned, causing eye melanoma to spread and become fatal.
Melanoma is a cancer normally associated with the skin, but it can occur anywhere in the body where pigment cells (melanocytes) are found, including the eye. Eye melanoma is the second most common form of melanoma. It doesn't always spread, but when it does, it's nearly always fatal.
Eye melanoma strikes about 2,000 adults in the United States each year. It is most common among people older than 50. It's fatal to about half of the people who are diagnosed.
Harbour and his colleague, Washington University geneticist Ann Bowcock, discovered a gene that can cause these eye cancers to spread.
The discovery happened this way:
For several decades, researchers have known of the existence of a defective gene that triggered the spread of eye melanoma. But they didn't know which of the tens of thousands of genes in our DNA might be the culprit. Genes are the parts of the DNA that contain the instructions for building the body, but genes make up only a small fraction of all of our DNA.
Until recently, researchers couldn't find the culprit gene because wading through the large amounts of mystery DNA -- DNA with no known function -- made the search impossible. A big breakthrough came earlier this decade when researchers found a way to distinguish between genes and mystery DNA.
"We've been able to weed out a lot of the noise," Harbour said. "We still had a needle in a haystack, but we made the haystack 95 percent smaller."
And within the last year, there it was, the defective gene. It was found through a process called exome capture and deep sequencing. It helps find genetic causes of diseases and it is also used by cancer researchers.
"Using that, we found the mutation very quickly," Harbour said, "a gene we'd been looking for for at least 20 years." When the gene malfunctions, it causes eye melanoma to spread.
Functioning properly, the gene appears to control important functions in the eye cells from which melanomas arise. When this gene is defective, cancerous cells learn how to escape the eye and spread to vital organs such as the liver.
With the discovery, Harbour said, his research team is identifying proteins that are affected by the mutation. That could lead to the design of new drugs to treat cancer patients.
"There are several ways this discovery could improve patient care," Harbour said. "If we could detect (genetic) mutations at an earlier stage, for example, we might be able to monitor a patient's blood for detectable melanoma cells as an early sign that they're developing metastatic disease.
"Also, these genetic discoveries give us new glimpses into how cancers work, and this may lead to new drugs that convert cancers like eye melanoma from a fatal disease to a chronic disease that can be managed."
Harbour said another benefit is that eye melanoma is a simpler form of cancer, less difficult to analyze. The simplicity may give insight into the workings of more complicated cancers, he said.
The research was supported by grants from the National Cancer Institute, National Eye Institute, National Institutes of Health, Barnes-Jewish Hospital Foundation, Kling Family Foundation, Tumori Foundation, Horncrest Foundation and Research to Prevent Blindness.
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