Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract, located mostly in the stomach (60%) and small intestine (35%). These tumors often have specific mutations in certain genes, and identifying these mutations is important for diagnosis, prognosis, and treatment decisions. A GIST mutation panel refers to a specific set of genetic tests conducted to identify mutations in genes associated with GISTs.

The most common mutations in GISTs occur in two genes: KIT Proto-Oncogene, Receptor Tyrosine Kinase (KIT) and Platelet-derived growth factor receptor A (PDGFRA). Approximately 80% of GISTs have a mutation in c-KIT and 5% to 10% of GISTs have a mutation in PDGFRA. PDGFRA mutations are mutually exclusive with c-KIT mutations but activate similar signal transduction pathways that support GIST oncogenesis. Mutations in these genes lead to the continuous activation of signaling pathways that promote cell growth and division, contributing to the development of GISTs. The location of c-KIT and PDGFRA mutations in GISTs is associated with the site of origin, histological phenotype, and treatment response to tyrosine kinase inhibitors (TKI, such as imatinib and sunitinib).

Other less common mutations can also occur, and in a subset of intestinal high-risk GISTs lacking c-KIT/PDGFRA mutations, 7% have a mutation in BRAF (v-raf murine sarcoma viral oncogene homolog B1). Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset.