Mutation analysis of C-KIT in patients with myelodysplastic syndromes without mastocytosis and cases of systemic mastocytosis

The proto-oncogene C-KIT encodes a tyrosine kinase receptor that is express ed on mast cells and haematopoietic stem cells and can show somatic mutatio ns in patients with mastocytosis. Only scattered information is available a bout mutations in C-KIT in patients with other myeloid neoplasms. Moreover, the prevalence of mutations in C-KIT in bone marrow specimens of individua ls with systemic mastocytosis is largely unknown. Using sequence analysis, we have screened cDNAs of the C-KIT domain encompassing codon 510-626 and c odon 763-858 in bone marrow (BM) mononuclear cells (MNCs) of patients with myelodysplastic syndromes (n = 28) and patients with systemic mastocytosis (n = 12) for the presence of mutations. Furthermore, restriction fragment l ength polymorphism analysis was applied for identification of the C-KIT 246 8A-->T and the C-KIT 1700T-->G mutation, as well as the C-KIT 1642A-->C pol ymorphism. All 11 patients with systemic indolent mastocytosis tested posit ive for C-KIT 2468A-->T. In contrast, no mutation was identified in the cas e of aggressive mastocytosis. Among patients with myelodysplastic syndromes , no patient showed a somatic mutation in C-KIT. The allele frequency for C -KIT 1642A-->C among the entire patient population was 0.038 and was 0.125 among age- and sex-matched healthy controls, Our data demonstrate that myel odysplastic syndromes without histological or cytological evidence of masto cytosis do not exhibit somatic mutations in exons 10, 11, 12, 16, 17 and 18 of C-KIT. In contrast, BM MNCs of patients with systemic indolent mastocyt osis were all positive for C-KIT 2468A-->T and negative for additional muta tions in these exons. The C-KIT 1642A-->C polymorphism is not associated wi th myelodysplastic syndrome or systemic mastocytosis.