What is the most common mutation in c-kit associated with systemic mastocytosis?

The most common mutation in c-kit associated with systemic mastocytosis is indeed found at codon 816, where a substitution of valine for aspartic acid occurs. This specific mutation is known as the D816V mutation and plays a critical role in the pathogenesis of systemic mastocytosis. It leads to the constitutive activation of the c-KIT receptor, a type of receptor tyrosine kinase that normally requires ligand binding for activation. The D816V mutation allows the receptor to remain active even in the absence of its ligand, promoting uncontrolled mast cell proliferation and survival, which is central to the development of systemic mastocytosis.

Understanding this mutation is essential for clinical practice, as it is often targeted in diagnostic testing and has implications for treatment decisions, particularly concerning the use of specific tyrosine kinase inhibitors that may be effective against this mutation. Thus, recognizing the role of the D816V mutation in systemic mastocytosis is crucial for understanding the disease's biology and potential therapeutic approaches.