Mastocytosis associated with a rare germline KIT K509I mutation displays a well-differentiated mast cell phenotype.

Background: Mastocytosis associated with germline KIT activating mutations is exceedingly rare. We report the unique clinicopathologic features of a patient with systemic mastocytosis caused by a de novo germline KIT K509I mutation.

Objectives: We sought to investigate the effect of the germline KIT K509I mutation on human mast cell development and function.

KIT GNNK splice variants: expression in systemic mastocytosis and influence on the activating potential of the D816V mutation in mast cells.

Stem cell factor-dependent KIT activation is an essential process for mast cell homeostasis. The two major splice variants of KIT differ by the presence or absence of four amino acids (GNNK) at the juxta-membrane region of the extracellular domain. We hypothesized that the expression pattern of these variants differs in systemic mastocytosis and that transcripts containing the KIT D816V mutation segregate preferentially to one GNNK variant.

Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis.

Cooperating genetic events are likely to contribute to the phenotypic diversity of KIT-D816V systemic mastocytosis. In this study, 44 patients with KIT-D816V systemic mastocytosis were evaluated for coexisting NRAS, KRAS, HRAS or MRAS mutations. Activating NRAS mutations were identified in 2 of 8 patients with advanced disease.