Download A targeted mutation panel covering genes implicated in MPN

A targeted mutation panel covering genes implicated in MPN demonstrated mutations in KIT D816V,
GATA1, FAM5C/BRINP3, and RUNX1. Next generation sequencing studies have shown RUNX1 to be
among the most commonly mutated genes in aggressive forms of mastocytosis and, in a univariate
analysis, the presence of this mutation is associated with an adverse prognosis (Jawhar
2016). Mutations in FAM5C/BRINP3 have not been previously reported in mast cell disease. Two
missense mutations were observed in GATA-1, a transcription factor involved in mast cell
ontogeny. While normal mast cells derive from common myeloid progenitor cells, in mice models,
downregulation of GATA-1 results in megakaryocyte-erythroid progenitors with the potential of mast
cell differentiation (Ghinassi 2007, Takemoto 2008).
Jawhar M et al. Additional mutations in SRSF2, ASXL1, and/or RUNX1 identify a high-risk group of
patients with KIT D817V+ advanced systemic mastocytosis. Leukemia 2016;30:136-143
Ghinassi B et al. The hypomorphic GATA1low mutation alters the proliferation/differentiation
potential of the megakaryocytic-erythroid progenitor. Blood 2007;109:1460-1471
Takemoto ET al. Mast cell transcriptional networks. Blood Cells Mol Dis. 2008;41:82-90.