26648 KIT p.Asp816Val Variant Analysis, Quantitative, Varies (KITQ)

​Diagnosing systemic mastocytosis

Whole blood or bone marrow specimens must arrive within 14 days of collection.

Specimen type is required to perform testing.

Blood and Bone Marrow Aspirate Collection Instructions:

1. Invert several times to mix.

2. Send specimen in original tube. DO NOT aliquot.

3. Label specimen with specimen type.

Some cases of systemic mastocytosis (SM)  may have sparse representation in bone marrow aspirate or blood samples containing too few neoplastic mast cells to successfully detect the KIT p.D816V (below limit of assay detection). Paraffin embedded tissues may be prone to sampling effects and DNA degradation, which may also compromise assay performance. Rare cases of SM may have other KIT mutations involving D816 (such as p.D816Y), or in other exon 17 codons that are not specifically targeted by this D816V ddPCR assay.

Assay sensitivity may be impacted by variability in tumor cell distribution or limited overall DNA quantity or quality.

​Systemic mastocytosis (SM) is a hematopoietic neoplasm that is now recognized as a distinct entity in the current World Health Organization and International Consensus Classifications. SM is characterized by a proliferation of neoplastic mast cells in the bone marrow and rarely in extramedullary sites. SM may present with variable degrees of clinical severity and can sometimes be associated with a non-mast cell hematologic neoplasm. SM is diagnosed using a combination of major and minor criteria, encompassing morphologic, biochemical and molecular genetic features. An important minor criterion is the presence of an activating somatic mutation in the KIT gene, encoding the tyrosine kinase receptor for stem cell factor, which is a critical growth factor in early myeloid cell proliferation and development. In SM, the most common KIT alteration is a missense change in exon 17 at codon 816, p.Asp816Val (D816V). Much less frequently, other missense mutations involving the D816 codon or adjacent amino acids are encountered and rarely, KIT genetic alterations can occur in other exons. A subset of acute myeloid leukemias (AML) with core-binding factor gene fusions can also acquire activating KIT gene mutations, including D816V in many cases. Detection of KIT D816V is critical to help establish a diagnosis of SM and is optimally determined by molecular testing. Because mast cell lesions are typically sparse and fibrotic in bone marrow and circulating tumor mast cells are in low abundance, highly sensitive and specific assays are required for optimal detection of KIT D816V. This can be achieved using quantitative allele-specific polymerase chain reaction (PCR) or droplet digital PCR (ddPCR) methods. The presence of KIT D816V mutation in the appropriate clinical and pathologic context is highly supportive of SM. In addition, although the D816V in SM is insensitive to targeted therapy with imatinib, other tyrosine kinase inhibitors such as avapritinib have demonstrated significant therapeutic efficacy in advanced SM, indicating that this mutation may also be a theranostic marker for these patients.

An interpretive report will be provided indicating the status as positive or negative for KIT p.Asp816Val (D816V).

KIT gene (NCBI accession NM_000222.3)​

​The test will be interpreted as positive or negative for KIT p.Asp816Val and a quantitative result will be included if positive.