Causes, Risk Factors, and Prevention of Gastrointestinal Stromal Tumors

About 80% of GISTs have a change in the KIT gene. This gene directs cells to make the KIT protein (also known as CD117), which causes the cells to grow and divide.

Usually, the KIT gene is inactive in interstitial cells of Cajal (ICCs), which GISTs develop from. The KIT gene is only active if there is a need for more ICCs. But the gene change in most GISTs causes the KIT gene to always be turned on, so the cells are always growing and dividing.

When KIT gene changes are inherited, the condition is called Familial GIST syndrome.

In about 5% to 10% of GISTs, the cancer cells have a change in the PDGFRA gene. This gene change causes ICCs to grow and divide more than usual, increasing the chance of developing a GIST.

Inherited gene changes in PDGFRA are a less common cause of Familial GIST syndrome.

SDH gene changes can be seen in GIST tumors that do not have the more common KIT or PDGFRA gene changes. Normally, the SDH gene helps control how cells produce energy, grow, and divide. However, changes in this gene can lead to uncontrolled cell growth and cancer.

Gene changes in SDH can be inherited or acquired.

Carney-Stratakis syndrome is an inherited SDH gene change that can increase the risk of GISTs and paragangliomas. These tumors may occur at a young age.

Carney triad is an acquired change in SDH gene expression that can increase the risk of GIST tumors, paragangliomas, and pulmonary chondromas.

This is a rare, inherited condition that leads to an increased risk of developing GISTs. People with this syndrome tend to develop GISTs at a younger age than when they usually occur. They are also more likely to have more than one GIST.

This syndrome is most often caused by a change in the KIT or PDGFRA gene, which causes ICCs to constantly grow and divide.

Sometimes people with familial GIST syndrome also have skin spots like those seen in patients with neurofibromatosis (discussed below).

For more information, see Familial GIST Syndrome.

This condition is caused by a defect in the NF1 gene. This gene change might be inherited from a parent, but in some cases, the change occurs before birth, without being inherited.

People affected by this syndrome often have many benign (noncancerous) nerve tumors, called neurofibromas, starting when they are young. These tumors form under the skin and in other parts of the body. These people also typically have tan or brown spots on the skin (café au lait spots).

People with NF1 have a higher risk of GISTs, most often in the small intestine, as well as some other types of cancer.

For more information, see Neurofibromatosis Type 1.

People with this rare inherited condition have an increased risk of GISTs, most often in the stomach, as well as nerve tumors called paragangliomas. GISTs often develop when these people are in their teens or 20s. They are also more likely to have more than one GIST.

This syndrome is caused by a change in one of the SDH genes, which is passed from parent to child.