Comparison of lesional skin c-KIT mutations with clinical phenotype in patients with mastocytosis

Abstract

Activating c-KIT mutations exist in a significant portion of patients with mastocytosis, but not all patients showed expression of these mutations. Except for V560G, the presence or absence of activating c-KIT mutations did not predict the extent of disease. These observations suggest that although activating c-KIT mutations are associated with mast cell growth, other genes probably play a role in the cause of mastocytosis.

Combined Nevus–Mastocytosis; Random Coincidence or Complex Biological Relationship?

“…14 A subset of patients with mastocytosis may harbor oncogenic mutations in other genes or other KIT variants, such as V560G; the latter has been suggested as an indicator of a more aggressive disease. 1 In general, although immunohistochemical expression of cKIT may be commonly seen in melanocytic neoplasms, KIT mutations are infrequent in cutaneous melanocytic tumors, only limited to rare cases of acral melanoma. 15 Accordingly, we believe it is unlikely that the melanocytic proliferation in this case being driven by a KIT mutation.…”

“…11 KIT functions as a proto oncogene that encodes a Type III receptor tyrosine kinase “KIT,” which is composed of extracellular, transmembrane, juxta membrane, and tyrosine kinase domains, and is normally activated by SCF. 1 It is expressed by germ cells, hematopoietic progenitor cells, mast cells, and melanocytes. 12 Activating mutations, most commonly a D816V gain-of-function mutation, 13 result in constitutive and SCF independent mast cell growth and proliferation.…”

“…Mastocytosis is characterized by an expanded monoclonal population of neoplastic mast cells often due to activating KIT mutations. 1 Systemic mastocytosis originates within the bone marrow with involvement of extra marrow sites, including skin and gastrointestinal tract. 2 Cutaneous mastocytosis is defined as a neoplastic mast cell proliferation limited to the skin without the bone marrow involvement or other diagnostic criteria of systemic mastocytosis (Table 1).…”

A case report of mast cell leukemia in a child and literature review

“…Прогрессирующее нарастание уровня триптазы при последовательных измерениях ассоциируется с прогрессией заболевания и неблагоприятным прогнозом. Несмотря на клинические и фенотипические различия детских и взрослых форм мастоцитоза, обе они являются клональными заболеваниями, в большинстве случаев ассоциированными с соматическими мутациями, усиливающими функции гена KIT (Somatic gain-of-function mutations) [19,[24][25][26][27].…”

“…Отсутствие какой бы то ни было мутации в кодоне 816 было детектировано у 58% обследованных детей [29]. Секвенирование всего гена KIT у детей, у которых не была выявлена мутация в кодоне 816 (D816V, D816Y, D816I), в 44% установило другие мутации, вовлекающие экзоны 8, 9, 11 и 13 [26,27].…”