Sensitive detection of KIT D816V in patients with mastocytosis

Abstract

Background: The 2447 A>T pathogenic variation at codon 816 of exon 17 (D816V) in the KIT gene, occurring in systemic mastocytosis (SM), leads to constitutive activation of tyrosine kinase activity and confers resistance to the tyrosine kinase inhibitor imatinib mesylate. Thus detection of this variation in SM patients is important for determining treatment strategy, but because the population of malignant cells carrying this variation is often small relative to the normal cell population, standard molecular detection methods can be unsuccessful. Methods: We developed 2 methods for detection of KIT D816V in SM patients. The first uses enriched sequencing of mutant alleles (ESMA) after BsmAI r..