What mutations are primarily associated with Gastrointestinal Stromal Tumors (GIST)?

Gastrointestinal Stromal Tumors (GISTs) are primarily associated with mutations in the c-KIT gene and, in some cases, mutations in the Platelet-derived growth factor receptor (PDGFRA) gene. The c-KIT gene encodes a receptor tyrosine kinase that plays a crucial role in regulating cell function, growth, and differentiation within the gastrointestinal tract. The majority of GISTs stem from interstitial cells of Cajal or precursor cells which typically express c-KIT.

The c-KIT mutations lead to constitutive activation of the receptor, driving tumorigenesis through unregulated cell proliferation and survival. In cases where c-KIT mutations are not identified, mutations in the PDGFRA gene can also be involved in the tumorigenesis of GISTs, although they are less common.

Understanding the molecular basis of GISTs is essential for targeted therapies, particularly the use of imatinib (Gleevec), which is a tyrosine kinase inhibitor that effectively blocks the activity of the mutated c-KIT and PDGFRA receptors, providing significant clinical benefit.

In contrast, the other options list mutations commonly associated with other types of cancers or conditions. For example, mutations in KRAS and BRAF are