Melanoma of the eye caused by two gene mutations

May 29, 2014
Melanoma of the Eye Caused by Two Gene Mutations
An untreated uveal melanoma tumor (left) covers entire eye of a mouse. A tumor treated with verteporfin (right) is much smaller and much of the structure of the mouse's eye is visible. Credit: UC San Diego School of Medicine

Researchers at the University of California, San Diego School of Medicine have identified a therapeutic target for treating the most common form of eye cancer in adults. They have also, in experiments with mice, been able to slow eye tumor growth with an existing FDA-approved drug.

The findings are published online in the May 29 issue of the journal Cancer Cell.

"The beauty of our study is its simplicity," said Kun-Liang Guan, PhD, professor of pharmacology at UC San Diego Moores Cancer Center and co-author of the study. "The genetics of this cancer are very simple and our results have clear implications for therapeutic treatments for the disease."

The researchers looked specifically at uveal . Uveal collectively refers to parts of the , notably the iris, that contain pigment cells. As with melanoma skin cancer, uveal melanoma is a malignancy of these melanin-producing cells.

Approximately 2,000 people in the United States are diagnosed with uveal melanoma each year. If the cancer is restricted to just the eye, the standard treatment is radiation and surgical removal of the eye. But uveal melanoma often spreads to the liver, and determining the metastatic status of the disease can be difficult. In cases of uveal melanoma metastasis, patients typically succumb within two to eight months after diagnosis.

Scientists have long suspected a genetic association with uveal melanoma because one of two gene mutations is present in approximately 70 percent of all tumors. Until this study, however, they had not identified a mechanism that could explain why and how these mutations actually caused tumors.

The work by Guan and colleagues unravels the causal relationship between the genetic mutations and tumor formation, and identifies a molecular pathway along which drugs might counterattack.

The two genes implicated – GNAQ and GNA11 – code for proteins (known as G proteins) that normally function as molecular on-off switches, regulating the passage of information from the outside to the inside of a cell.

In their experiments, the scientists showed that mutations in these genes shift the G proteins to a permanent "on" or active status, which results in over-activation the Yes-associated protein (YAP). The activation of the YAP protein induces and inhibits cell death, causing malignancies.

Earlier research by other scientists has shown that the drug verteporfin, used to treat formation in the eye, acts on the YAP pathway inhibiting the protein's YAP function.

In experiments with mice, the UC San Diego-led team showed that verteporfin also suppresses the growth of uveal melanoma tumors derived from human tumors.

"We have a that is caused by a very simple genetic mechanism," Guan said. "And we have a drug that works on this mechanism. The clinical applications are very direct."

Explore further: New drug improves progression-free survival, shrinks tumors in rare cancer for first time

Related Stories

New drug improves progression-free survival, shrinks tumors in rare cancer for first time

June 1, 2013
The experimental drug selumetinib is the first targeted therapy to demonstrate significant clinical benefit for patients with metastatic uveal melanoma, according to new Memorial Sloan-Kettering Cancer Center research presented ...

Gene in eye melanomas linked to good prognosis

January 16, 2013
Melanomas that develop in the eye often are fatal. Now, scientists at Washington University School of Medicine in St. Louis report they have identified a mutated gene in melanoma tumors of the eye that appears to predict ...

Drug may slow spread of deadly eye cancer

November 28, 2011
A drug commonly used to treat seizures appears to make eye tumors less likely to grow if they spread to other parts of the body, according to researchers at Washington University School of Medicine in St. Louis.

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.