Expert Reviewed By: Dr. Brandon Colby MD
Gastrointestinal stromal tumors (GISTs) are a rare type of cancer that develops in the gastrointestinal tract, primarily affecting the stomach and small intestine. Familial GISTs are even rarer, with cases arising due to inherited genetic mutations. This article aims to provide an overview of the molecular genetics of familial GISTs, highlighting the importance of genetic testing in their diagnosis and management.
Understanding Familial Gastrointestinal Stromal Tumor
While most GISTs are sporadic, meaning they occur randomly without a known cause, a small percentage of cases are familial, resulting from inherited genetic mutations3. These mutations increase the risk of developing GISTs and may also be associated with other conditions, such as mastocytosis and seminoma2.
Diagnosing Familial Gastrointestinal Stromal Tumor
Diagnosing familial GISTs requires a combination of clinical evaluation, imaging studies, and molecular genetic testing. Molecular genetic testing is particularly important, as it can identify specific gene mutations that cause the disease and help guide treatment decisions3.
Key Genetic Mutations in Familial GISTs
Several genetic mutations have been associated with familial GISTs, including mutations in the KIT, PDGFRA, and SDHA genes3. A novel germline mutation in the KIT gene, p.Lys558Asn (K558N), has been identified in a patient with multiple GISTs, mastocytosis, and seminoma2. Additionally, germline variants in the SDHA gene have been found to be highly frequent in SDHA-deficient GISTs4.
Genetic Testing for Familial GISTs
Genetic testing for familial GISTs typically involves analyzing DNA samples from blood or saliva to identify mutations in the KIT, PDGFRA, and SDHA genes3. Identifying these mutations can confirm a diagnosis of familial GIST and provide valuable information for treatment planning.
Using Genetic Testing in the Management of Familial GISTs
Genetic testing plays a crucial role in the management of familial GISTs, as it can inform treatment decisions and help monitor the disease's progression. Additionally, genetic testing can be used to identify at-risk family members and guide surveillance strategies for mutation carriers and their relatives4.
Guiding Treatment Decisions
Identifying specific gene mutations in familial GISTs can help determine the most effective treatment options. For example, patients with KIT or PDGFRA mutations may benefit from targeted therapies, such as imatinib, while those with SDHA mutations may require alternative treatments3.
Monitoring Disease Progression
Genetic testing can also be used to monitor the disease's progression and response to treatment. By tracking changes in the levels of specific gene mutations, clinicians can assess whether a patient's tumor is shrinking, growing, or remaining stable3.
Surveillance for Mutation Carriers and Relatives
Individuals who carry genetic mutations associated with familial GISTs are at an increased risk of developing the disease. Genetic testing can help identify these individuals, allowing for regular surveillance and early detection of GISTs4. Additionally, relatives of mutation carriers can also benefit from genetic testing and surveillance, as they may be at risk of inheriting the disease-causing mutations.
In conclusion, understanding the molecular genetics of familial GISTs is essential for accurate diagnosis and effective management. Genetic testing plays a central role in identifying disease-causing mutations, guiding treatment decisions, monitoring disease progression, and providing surveillance for at-risk individuals and their families.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)