蜜桃传媒

Researchers do not know exactly what causes most gastrointestinal stromal tumors (GISTs). But great progress has been made in learning how certain changes in DNA can cause normal cells to become cancer cells.

DNA is the chemical in our cells that makes up our genes, which control 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, divide, and stay alive are called oncogenes. 
• Genes that normally keep cell growth under control, repair mistakes in DNA, or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes that keep oncogenes turned on, or that turn off tumor suppressor genes. These types of gene changes can lead to cells growing out of control.

Gene changes that can lead to GISTs

The gene changes that lead to most GISTs are now understood, but it’s still not clear why these changes occur. There are no known lifestyle-related or environmental risk factors for GIST. Some of the gene changes that lead to GISTs 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.

A small number of families have GISTs that are caused by a gene mutation passed down from parent to child. (See Gastrointestinal Stromal Tumor Risk Factors.) But most gene mutations related to GISTs are not inherited. These changes occur for no apparent reason, and are called acquired or sporadic.

Changes in KIT or PDGFRA genes

In most people with GISTs, the cancer cells have a change in the KIT oncogene. 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 are the cells in the walls of the GI tract from which GISTs develop. The KIT gene is only active if there is a need for more ICCs. But in most GISTs the KIT gene is mutated. It is always active, so the cells are always growing and dividing.

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

Most GISTs have changes in either the KIT or the PDGFRA gene, but not both.

Other gene changes

A small number of GISTs, especially those in children, do not have changes in either of these genes. Many of these tumors have changes in one of the SDH genes. Researchers are still trying to determine what other gene changes can lead to these cancers.

As doctors have learned more about the gene and protein changes in GIST cells, they have been able to use this information to help diagnose and treat these cancers. (See Targeted Therapy for Gastrointestinal Stromal Tumors.)