Abstract
Mastocytosis Is characterized by accumulations of mast cells in various organs1. Most cases are indolent and confined to the skin, where discrete mast cell infiltrates are associated with increased epidermal melanin, a clinical picture known as urticaria pigmentosa (UP). Other forms of mastocytosis combine UP with aggressive involvement of other organs or with haematologic abnormalities1–4. It is not known whether all forms of mastocytosis are true neoplasms or whether some might represent reactive hyperplasias5–7. The c-KIT proto-oncogene encodes a type III receptor tyrosine kinase (KIT) that is critical to the development and survival of mast cells and melanocytes8–11. The ligand for KIT (KL) can stimulate mast cell development, proliferation, and mediator release9,12–17, as well as melanocyte proliferation and pigment production18–20. To determine the role of c-KIT in the pathogenesis of mastocytosis, we examined tissue and cells isolated from a patient with UP and aggressive systemic mastocytosis with massive splenic involvement. We found a mutation that results in constitutive activation and expression of c-KIT in mast cells of both skin and spleen. This is the first in situ demonstration of an activating c-KIT mutation in neoplastic cells. It also demonstrates the clonal and neoplastic nature of this form of mastocytosis.
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Longley, B., Tyrrell, L., Lu, SZ. et al. Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm. Nat Genet 12, 312–314 (1996). https://doi.org/10.1038/ng0396-312
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DOI: https://doi.org/10.1038/ng0396-312
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