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 that carries the instructions for nearly everything our cells do. We look like our parents because they are the source of our DNA. But DNA affects more than the way we look. Some genes (parts of our DNA) contain instructions for controlling when cells grow and divide.

Every time a cell prepares to divide into 2 new cells, it must duplicate its DNA. This process is not perfect and, sometimes errors occur, especially if the cells are growing rapidly. These copying errors result in a defect (or mutation) in a gene.

Certain genes that promote cell growth and division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. We know that cancers can be caused by DNA mutations (defects) that turn on oncogenes or turn off tumor suppressor genes.

Some people with certain types of cancer have DNA mutations they inherited from a parent, which increased their risk for the disease. There are a few families that have GISTs caused by a mutation passed down from parent to child. But most DNA mutations related to GISTs are not inherited. These mutations occur for no apparent reason, and are called sporadic.

We do not know the exact cause of GIST. However, we do know that 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 leads to the formation of a protein called KIT. This protein causes the cell to grow and divide. Usually the c-kit gene is inactive. It is only activated 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 of the families that have many members with GISTs, doctors have found inherited mutations of the c-kit gene.

In some GISTs, a different gene mutation causes the cell to make too much of a protein called PDGFRA. This has the same effect on the cell as does KIT.

These proteins (KIT and PDGFRA) act as enzymes called tyrosine kinases. These are important in the diagnosis and treatment of GIST (see the section "How Are Gastrointestinal Stromal Tumors Treated?").

Last Medical Review: 05/11/2009
Last Revised: 05/11/2009