Gastrointestinal Stromal Tumor (GIST)

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Causes, Risk Factors, and Prevention TOPICS

Do we know what causes gastrointestinal stromal tumors?

We do not know exactly what causes most gastrointestinal stromal tumors (GISTs). But in recent years, scientists have made great progress in learning how certain changes in DNA can cause normal cells to become cancerous. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes control when cells grow and divide into new cells. Certain genes that help cells grow and divide are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

A few families have gastrointestinal stromal tumors (GISTs) caused by a DNA mutation passed down from parent to child. But most DNA mutations related to GISTs are not inherited. These changes occur for no apparent reason, and are called acquired or sporadic.

The cancer cells of most patients with GIST have a change in an oncogene called c-kit. The c-kit gene is found in all cells of the body. It directs the cell to make a protein called KIT, which causes the cell to grow and divide. Usually the c-kit gene is inactive. It is only active if there is a need for more interstitial cells of Cajal (ICCs). In most GISTs the c-kit gene is mutated and is always active. This may explain why the cancer forms. The cells are always growing and dividing. In some families that have many members with GISTs, doctors have found inherited mutations of the c-kit gene.

In about 5% to 10% of GISTs, the cancer cells have mutation in a different gene called PDGFRA, which causes the cell to make too much of a different protein (also called PDGFRA). This has the same effect on the cell as does KIT.

Most GISTs have changes in either the c-kit or the PDGFRA gene, but not both. A small number of GISTs do not have changes in either of these genes. Researchers are still trying to determine what gene changes lead to these cancers.

The gene changes that lead to most GISTs are now understood, but it’s still not clear what might cause these changes. There are no known lifestyle-related or environmental causes of GIST. Some might have causes that haven’t been found yet, but many of these changes may just be random events that sometimes happen inside cells that unfortunately lead to cancer.

As doctors have learned more about the gene and protein changes common in GIST cells, they have been able to use this information to help diagnose and treat these cancers (see the section called “Targeted therapy”).


Last Medical Review: 12/11/2012
Last Revised: 02/26/2013