Familial GIST

Approved by the Cancer.Net Editorial Board, 03/2020

What is familial GIST?

Familial GIST is a hereditary syndrome that increases a person’s risk of developing GIST. A gastrointestinal stromal tumor (GIST) is a type of tumor that is found in the gastrointestinal (GI) tract, which includes the esophagus, stomach, gallbladder, liver, small intestine, colon, rectum, and lining of the gut. The GI tract plays a central role in digesting food and liquid, and processing waste. GISTs start in the interstitial cells of Cajal (ICC) located in the GI tract wall.

GISTs are different from other, more common types of GI tumors because of the type of tissue in which they start. GISTs belong to a group of cancers called soft tissue sarcoma

People with familial GIST can have several GISTs at the time of diagnosis. In familial GIST, tumors appear most often in the stomach and small intestine. The tumors are often diagnosed between the age of 25 and 45. For comparison, the age when non-inherited GIST, also called sporadic GIST, tends to develop is typically after age 50. All GISTs have the potential to become cancerous and spread to other parts of the body. However, tumors caused by familial GIST may spread elsewhere less often than sporadic GIST.

As it grows, any GIST can cause symptoms such as:

  • Pain or discomfort in the abdomen

  • A mass in the abdomen that you can feel with your hand

  • Nausea and vomiting

  • Vomiting blood or having blood in the stool

  • Fatigue due to anemia, which means your red blood cell counts are low

People with familial GIST often have additional signs or symptoms. These can include:

  • Difficulties with occasional abdominal pain and episodes of constipation and diarrhea, which can be mistaken for irritable bowel syndrome in some people

  • Dark patches of skin on the body, known as skin hyperpigmentation, that often become visible in childhood or during puberty. These are most commonly found on the hands and feet, more than in the armpit or groin areas.

  • A skin condition called urticaria pigmentosa, which results in raised patches of brownish skin that sting or itch. This condition may also increase the risk of skin infections in some people.

  • Skin moles

  • Difficulty swallowing, known as dysphagia

  • Excessive ICC growth in the GI tract, called hyperplasia, which may be the cause of multiple GISTs developing as well as some of the irritable bowel syndrome-like features of familial GIST (see above; first bullet)

What causes familial GIST?

Familial GIST is passed from generation to generation in a family. The most common genes affected and the syndromes they cause are:

  • KIT and PDGFR – primary familial GIST syndrome

  • Neurofibromin (NF1) - Neurofibromatosis 1

  • Succinate dehydrogenase (SDH) - Carney-Stratakis dyad/SDH-deficient GIST

Researchers continue to look for specific genes that may be related to the development of familial GIST and which may be used to help decide the patient’s treatment plan. 

How is familial GIST inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. Familial GIST follows an autosomal dominant inheritance pattern. In autosomal dominant inheritance, a mutation happens in only 1 copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (meaning each person’s test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than an average risk.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. PGD has been in use for over 2 decades and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is familial GIST?

Overall, GIST is diagnosed in about 4,000 to 6,000 people in the United States each year. However, familial GIST is rare. There are an estimated 50 to 100 known families who have multiple family members who develop GIST across the world. However, as researchers continue to learn more about GIST and familial GIST, it is possible this number may increase.

How is familial GIST diagnosed?

If symptoms and signs of GIST appear, your doctor will ask you about your medical history, perform a physical exam, and recommend imaging tests to confirm GIST. Those tests may include barium x-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans.

If a mass is found, your doctor will recommend a biopsy. This means removing a small piece of tissue so that it can be examined under a microscope. The specific procedure for the biopsy will depend on a tumor’s location. An endoscopy, a procedure in which a thin tube with a camera is inserted into the body to see the GI tract, may be done. During this procedure, tissue samples can be removed for examination. Sometimes, GIST is found unexpectedly during testing or surgery for an unrelated health condition.

Familial GIST is considered when:

  • A person in your family had GIST before age 50

  • A person in your family developed more than 1 GIST

  • 2 or more close relatives were diagnosed with GIST

  • A person in your family with GIST also has a close relative with another rare tumor type

  • A person in your family with GIST also has NF1, multiple moles, or uncommon skin issues

Once a diagnosis of GIST is confirmed, genetic testing may be recommended if familial GIST is suspected. This means taking a sample of the patient’s DNA through a saliva swab or blood test. A physician or genetic counselor can review your personal and family health history to help determine if you should consider this type of testing.

It is important to note that genetic testing for familial GIST is still evolving. There may be genes other than those listed, such as KIT or PDGFRA, that cause the syndrome, and the current tests may not identify all families who have mutations in those specific genes.

What are the estimated cancer risks associated with familial GIST?

Familial GIST is associated with an increased risk of developing 1 or more GISTs. A mutation in the KIT gene is particularly associated with a high risk of developing GIST during a person’s lifetime. However, not everyone with a known mutation will develop GIST. It is not known if people with primay familial GIST have an increased risk of other specific types of tumors.

What are the screening options for people with familial GIST before a tumor develops?

Currently, there is no standard screening for people who have a known genetic mutation but who have not developed a tumor. Your doctor will work with you to determine a personal screening plan that is best for you. Screening options may change over time as new technologies are developed and more is learned about familial GIST. It is important to talk with your doctor about appropriate screening tests. In general, different types of scans, such as CT scan, MRI scan, or endoscopy to look at the stomach from the inside with a camera, are ways that doctors can monitor people for the development of GIST.

Learn more about what to expect when having common tests, procedures, and scans.

What are ways of treating tumors related to familial GIST?

Treatment options and recommendations depend on several factors, including where the tumor(s) is located, if or where the disease has spread, and whether tumors are affecting other parts of the body. As noted above, there is some evidence that familial GIST spreads slower than sporadic GIST and this may affect treatment decisions. Given the rare nature of the disease, patients are encouraged to talk with doctors who have specific expertise in this area of medicine.

The 2 main types of treatment used are: surgery and targeted therapy. Surgery is the removal of a tumor and surrounding tissue during an operation. Targeted therapy is a treatment that targets the tumor’s specific genes, proteins, or tissue environment that contributes to the tumor’s growth or survival. The treatment, which is given alone or in combination with surgery, blocks the growth and spread of tumor cells while limiting damage to normal cells. Imatinib (Gleevec) is often the first drug used to treat GIST as it targets both KIT and PDGFRA. Other drugs, such as sunitinib (Sutent), regorafenib (Stivarga) and avapritnib (Ayvakit), may also be used. Learn more about treatment options for a person with GIST. In addition, finding new targeted therapy drugs and other treatments for GIST is an active area of research through clinical trials.

Questions to ask the health care team

If you are concerned about your risk of developing cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of developing GIST?

  • What is my risk of other types of cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

If you are concerned about your family history and think your family may have familial GIST, consider asking the following questions:

  • Does my family history increase my risk of GIST?

  • Should I meet with a genetic counselor or other genetics specialist?

  • Should I consider genetic testing?

  • Are there options for screening if familial GIST is suspected?

Related Resources

The Genetics of Cancer

Genetic Testing

What to Expect When You Meet With a Genetic Counselor

Collecting Your Family Cancer History

Sharing Genetic Test Results with Your Family

Family Genetic Testing Q&A

More Information

GIST Support International

The Life Raft Group

National Cancer Institute

To find a genetic counselor in your area, ask your health care team or visit the following website: 

National Society of Genetic Counselors