Detection of the KIT D816V mutation in peripheral blood of systemic mastocytosis: diagnostic implications

Mod Pathol. 2015 Aug;28(8):1138-49. doi: 10.1038/modpathol.2015.72. Epub 2015 Jun 12.


Recent studies have found the KIT D816V mutation in peripheral blood of virtually all adult systemic mastocytosis patients once highly sensitive PCR techniques were used; thus, detection of the KIT D816V mutation in peripheral blood has been proposed to be included in the diagnostic work-up of systemic mastocytosis algorithms. However, the precise frequency of the mutation, the biological significance of peripheral blood-mutated cells and their potential association with involvement of bone marrow hematopoietic cells other than mast cells still remain to be investigated. Here, we determined the frequency of peripheral blood involvement by the KIT D816V mutation, as assessed by two highly sensitive PCR methods, and investigated its relationship with multilineage involvement of bone marrow hematopoiesis. Overall, our results confirmed the presence of the KIT D816V mutation in peripheral blood of most systemic mastocytosis cases (161/190; 85%)--with an increasing frequency from indolent systemic mastocytosis without skin lesions (29/44; 66%) to indolent systemic mastocytosis with skin involvement (124/135; 92%), and more aggressive disease subtypes (11/11; 100%)--as assessed by the allele-specific oligonucleotide-qPCR method, which was more sensitive (P<.0001) than the peptide nucleic acid-mediated PCR approach (84/190; 44%). Although the presence of the KIT mutation in peripheral blood, as assessed by the allele-specific oligonucleotide-qPCR technique, did not accurately predict for multilineage bone marrow involvement of hematopoiesis, the allele-specific oligonucleotide-qPCR allele burden and the peptide nucleic acid-mediated-PCR approach did. These results suggest that both methods provide clinically useful and complementary information through the identification and/or quantification of the KIT D816V mutation in peripheral blood of patients suspected of systemic mastocytosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / pathology
  • Bone Marrow Examination
  • Cell Lineage
  • DNA Mutational Analysis / methods*
  • Exons
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Hematopoiesis / genetics
  • Humans
  • Mast Cells / pathology
  • Mastocytosis, Systemic / blood
  • Mastocytosis, Systemic / diagnosis*
  • Mastocytosis, Systemic / genetics*
  • Mutation*
  • Phenotype
  • Polymerase Chain Reaction / methods*
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-kit / blood
  • Proto-Oncogene Proteins c-kit / genetics*
  • Severity of Illness Index
  • Spain


  • Genetic Markers
  • Proto-Oncogene Proteins c-kit