How Gene Mutations in GNAQ and GNA11 Trigger Eye Cancer: Understanding Uveal Melanoma in Simple Terms

How Gene Mutations in GNAQ and GNA11 Trigger Eye Cancer: Understanding Uveal Melanoma in Simple Terms Published: July 19, 0225 | By: OcularCancer.com Uveal melanoma is a rare kind of cancer that starts in the eye, specifically in a part called the uvea. The uvea is the middle layer of the eye and includes the iris (the colored part of your eye), the ciliary body (which helps your eye focus), and the choroid (a layer full of blood vessels that feeds the eye). This type of cancer develops from cells called melanocytes, which are the same types of cells that give our skin and eyes their color. When these melanocytes inside the eye start to grow out of control, they can form a tumor, leading to uveal melanoma. This disease is different from the more common skin melanoma, which is often caused by too much sun exposure. Uveal melanoma happens inside the eye and has different causes that aren't related to sunlight.

Scientists have discovered that in most people with uveal melanoma, there are changes, called mutations, in two specific genes named GNAQ and GNA11. Genes are like instruction manuals that tell our cells how to work. The GNAQ and GNA11 genes normally give instructions to make proteins that help control how cells grow, move, and respond to signals from the body. These proteins act like little switches that turn certain cell functions on and off at the right times. But when there's a mutation in one of these genes, the switch can get stuck in the "on" position. That means the cell keeps getting the message to grow and divide, even when it shouldn't. Over time, this nonstop growth can lead to the formation of a tumor.

When these gene mutations happen in the eye's melanocytes, they start sending powerful growth signals inside the cell. One of these signals goes through a chain of proteins known as the MAPK pathway. You can think of this like a series of dominos - when the first one falls, it pushes the next, and the signal keeps going until it reaches the part of the cell that controls growth. This MAPK pathway tells the cell to keep growing and not to die, even when it should. Another important signal that’s turned on by GNAQ and GNA11 mutations involves a protein called YAP. Normally, YAP helps control whether cells grow or stay the same. But in uveal melanoma, the YAP protein goes into the center of the cell, the nucleus, and turns on other genes that help the cell stay alive and divide. Together, these faulty signals lead to uncontrolled growth, which is what causes cancer to develop.

Even though we know that GNAQ and GNA11 mutations are a big part of what causes uveal melanoma, doctors don't yet have a way to directly fix these faulty genes. The proteins made by these mutated genes don’t have the right shape or surface that would allow medicine to easily block them. This makes them what scientists call “undruggable.” However, researchers are trying to find medicines that can stop the signals these mutated genes send out. For example, they are testing drugs that block parts of the MAPK or YAP pathways, which might help slow down or stop the cancer. Some of these drugs have been tested in clinical trials, but so far, the results have only been helpful in a small number of patients.

Although the mutations in GNAQ and GNA11 are very important for starting uveal melanoma, they don’t tell us how dangerous the cancer is or whether it will spread to other parts of the body. Other genetic changes, like the loss of a gene called BAP1 or changes in certain chromosomes, are more closely linked to the risk of the cancer spreading, especially to the liver. Still, finding GNAQ or GNA11 mutations in a tumor helps doctors confirm that the tumor started in the uvea and not somewhere else in the body.

In simple terms, the GNAQ and GNA11 mutations are like broken light switches that keep telling the eye’s pigment cells to grow, even when they should stop. This constant message causes the cells to grow into a tumor. While we don’t yet have a cure that targets these specific mutations, understanding them gives doctors and researchers a clearer picture of how uveal melanoma begins, which is an important step toward finding better treatments in the future.