Changes to KIT Mutation Analysis; Testing Now Available in the
Molecular Pathology Laboratory

Effective immediately, KIT Mutation Analysis by DNA sequencing will be provided in the Molecular Pathology Laboratory by the Department of Pathology and replace the c-KIT DNA sequencing mail-out test.

KIT (also known as c-KIT) belongs to a family of type III receptor tyrosine kinases, which includes platelet-derived growth factor receptor-α (PDGFRA), macrophage colony-stimulating-factor receptor (CSF1R) and Fl cytokine receptor (FLT3).  Activating mutations in KIT result in ligand-independent receptor dimerization and autophosphorylation, leading to alternations in apoptosis, cell proliferation and differentiation through the MAP kinase pathway as well as the PI3K-AKT pathway.   KIT mutations are seen in 70–80% of gastrointestinal stromal tumors (GISTs), ~95% mastocytosis, 25% germ cell tumor, 2% melanoma and a subset of acute myeloid leukemia (AML).  The location and type of KIT mutations are associated with prognosis and response to imatinib therapy.

Testing of KIT mutations can be utilized:
1. To assist in diagnosis of GIST, melanoma and AML.
2. To assist in therapy selection for GIST and melanoma
3. To assist in prognosis of GIST and AML

Specimen type: tumor tissue (fresh or formalin fixed paraffin embedded), whole blood (EDTA anti-coagulated; pink or lavender top tube), or bone marrow aspirate (EDTA anti-coagulated; pink or lavender top tube).

Method: DNA sequencing of targeted exons.  The sensitivity of the assay is 20% of mutant allele in the background of wild type allele.

Two separate tests are available from the UIHC Molecular Pathology Laboratory based on the relative frequency of mutations for the different diseases:

NOTE: PCR testing for KIT D816V mutation seen in mast cell disease will continue to be mailed out and can be ordered separately (see KITMAST, EPIC Code: LAB7567).

Questions concerning testing can be directed to Deqin Ma, MD, PhD (ext. 4-5700), Jonathan Heusel, MD, PhD (ext. 6-8217), or Aaron Bossler, MD, PhD (ext. 4-9566).