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, 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 and divide are called oncogenes
  • Genes that help 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.

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 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.

A few families have gastrointestinal stromal tumors (GISTs) 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

The cancer cells of most patients with GISTs have a change in an oncogene called KIT. This gene directs cells to make a protein called KIT, which causes the cells to grow and divide. Usually the KIT gene is inactive in interstitial cells of Cajal (ICCs), which are the cells 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 and is always active, so the cells are always growing and dividing.

In about 5% to 10% of GISTs, the cancer cells have mutation in a different gene called PDGFRA, which causes the cells to make too much of a different protein (also called PDGFRA). 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.)

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Casali PG, Dei Tos AP, Gronchi A. Chapter 55: Gastrointestinal Stromal Tumor. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.

National Cancer Institute. Physician Data Query (PDQ). Gastrointestinal Stromal Tumors Treatment. 2017. Accessed at www.cancer.gov/types/soft-tissue-sarcoma/hp/gist-treatment-pdq on April 17, 2017.

Last Medical Review: April 4, 2014 Last Revised: February 8, 2016

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.