26434 KIT Asp816Val Mutation Analysis, Varies (KITVS)

C-KIT

D816V

Systemic Mastocytosis Mutation

​Diagnosing systemic mastocytosis using blood or bone marrow specimens

Specimen Type: Peripheral blood

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

3. Label specimen as blood.

Specimen Stability: Ambient (preferred) 7 days; Refrigerate 7 days

Specimen Type: Bone marrow

1. Invert several times to mix bone marrow.

2. Send specimens in original tube. Do not aliquot.

3. Label specimen as bone marrow.

Specimen Stability: Ambient (preferred) 7 days; Refrigerate 7 days

Specimen Type: Extracted DNA from blood or bone marrow

1. Label specimen as extracted DNA from blood or bone marrow.

2. Provide indication of volume and concentration of DNA.

Specimen Stability Information: Frozen (preferred), Refrigerated.

Gross hemolysis

Moderately to severely clotted

 Bone marrow biopsies

 Paraffin-embedded bone marrow clots

 Paraffin-embedded tissue

Some systemic mastocytosis cases may have the variation only in mast cells. Since these cells rarely circulate in blood and are difficult to obtain in significant numbers from bone marrow aspirate specimens, false-negative results may occur if neoplastic cells are present below the sensitivity of the assay (fewer than 0.1% altered alleles).

The test is qualitative only. Reliable quantitative results cannot be issued.

Systemic mastocytosis is a hematopoietic neoplasm that can be included in the general category of chronic myeloproliferative disorders (CMPD). These neoplasms are characterized by excessive proliferation of 1 or more myeloid lineages, with cells filling the bone marrow and populating other hematopoietic sites. In systemic mastocytosis, mast cell proliferation is the defining feature, although other myeloid lineages and B cells are frequently part of the neoplastic clone.

Function-altering point alterations in KIT, a gene coding for a membrane receptor tyrosine kinase, have been found in myeloid lineage cells in the majority of systemic mastocytosis cases. The most common KIT alteration is an adenine to thymine base substitution (A>T) at nucleotide position 2447, which results in an aspartic acid to valine change in the protein (Asp816Val). Much less frequently, other alterations at this same location are found, and occasional cases with alterations at other locations have also been reported. Variations at codon 816 are believed to alter the protein such that it is in a constitutively activated state. The main downstream effect of KIT activation is cell proliferation.

Detection of a variant at codon 816 is included as one of the minor diagnostic criteria for systemic mastocytosis in the World Health Organization classification system for hematopoietic neoplasms and is also of therapeutic relevance, as it confers resistance to imatinib, a drug commonly used to treat CMPD. It is now clear that individual mast cell neoplasms are variable with respect to the number of cell lineages containing the variant; some having positivity only in mast cells and others having positivity in additional myeloid and even lymphoid lineages. The alteration has not been reported in normal tissues.

​The test will be interpreted as positive or negative for KIT Asp816Val.