c-KIT Mutation, Liquid Tumor

Use: c-KIT is a proto-oncogene that encodes a type III transmembrane tyrosine kinase. c-KIT and its ligand stem cell factor have a key role in survival, proliferation, differentiation, and functional activation of hematopoietic progenitor cells. c-KIT mutations are reported in nearly all systemic mastocytosis, 20% to 40% core-binding factor (CBF) acute myeloid leukemia (AML), and approximately 20% high-grade myelodysplastic syndrome (MDS) and MDS-derived AML. c-KIT mutation in AML confers increased risk of relapse and decreased overall survival. Tyrosine kinase inhibitor, such as imatinib, has been evaluated to treat systemic mastocytosis and c-KIT-positive AML and MDS, and it was found effective as a single reagent or combination therapy.

Limitations: Genomic DNA was purified from the provided specimen. Exons 8 and 17 of c-KIT gene coding were subjected to PCR amplification and bidirectional sequencing in duplicate to identify sequence variations. This assay has a sensitivity to detect approximately 10% population of cells containing the c-KIT mutations in a background of nonmutant cells. This assay will not detect the mutation below the sensitivity of the assay. Molecular-based testing is highly accurate but, as in any laboratory test, rare diagnostic errors may occur.

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).

Methodology: Polymerase chain reaction (PCR) and DNA sequencing