Novel methods for the sensitive detection of c-KIT D816V and other Exon 17 mutations in patients with mastocytosis

Abstract

Abstract Background The mutation A2447T (D816V) in the c-kit gene found in systemic mastocytosis (SM) leads to constitutive activation of tyrosine kinase activity and confers resistance to the tyrosine kinase inhibitor imatinib mesylate (IM) at standard doses. Other c-kit point mutations affecting codon 816 have been reported to have a similar dose-response to IM as the D816V mutation. Molecular studies of SM are difficult to perform as the population of malignant cells in the available tissues which carry the mutation is often small relative to the normal cell population. Using methods like direct sequencing is not ideal as the mutant signal is often obscured b..