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

The most common activating point mutation in c-kit associated with systemic mastocytosis is the substitution of valine for aspartic acid at codon 816. This mutation is a critical factor in the pathogenesis of systemic mastocytosis, where the c-kit receptor, which is a crucial player in hematopoiesis and mast cell growth, becomes constitutively activated.

In systemic mastocytosis, this particular mutation leads to the deregulation of mast cell development and function, resulting in excessive mast cell proliferation. The mutation alters the kinase activity of the c-kit receptor, contributing to the disease's manifestation. This is why the identification of the specific mutation at codon 816 is significant in the context of diagnosis and treatment.

Understanding this mutation allows healthcare providers to tailor therapeutic strategies such as using targeted therapies that inhibit the activity of the c-kit receptor, ultimately helping to manage symptoms and disease progression in patients with systemic mastocytosis.