KIT by Sequencing

Formalin-fixed, paraffin-embedded tissue blocks; fixed in 10% neutral-buffered formalin for at least 6 hours, and not more than 48 hours. Tissue should be prepared in sections between 4 to 6 microns thick. EDTA decal specimens and cytology smears are acceptable. Minimum 1mL of bone marrow aspirate or peripheral blood in green top sodium heparin (preferred) or purple top EDTA (acceptable). Contact FISH lab for fresh tissue or other fluid.

Approximately 80% of GIST have a mutation in the gene encoding the KIT receptor tyrosine kinase; another 5%–10% of GIST have a mutation in the gene encoding the related PDGFRA receptor tyrosine kinase. The presence and type of KIT and PDGFRA mutations are not strongly correlated with prognosis. About 10%–15% of GIST lack mutations in KIT or PDGFRA. The vast majority of these GIST have functional inactivation of the SDH complex, which can be detected by lack of expression of SDHB on IHC. KIT_D816 mutations are reported in greater than 80% of adults with systemic mastocytosis.

KIT activation results in increased intracellular signaling through several pathways including PI3K, MAPK and STAT, ultimately leading to cell proliferation and survival. Activating KIT mutations occur in 80 - 90% of GISTs and are distributed over multiple exons with different frequencies (exons 11 (66.1%), exon 9 (13%), exon 13 (1.2%), and exon 17 (0.6%)) (PMID: 15365079, 17268243, 11719439). There are at least eight small molecule tyrosine kinase inhibitors (TKIs) targeting KIT that have been approved by the US Food and Drug Administration (FDA) which could be used in GIST, Melanoma, and other cancer types. KIT mutation status carries prognostic and therapeutic impact in AML cases.

Pathology Report

Room temperature, express mail if not on courier service

Tissue not verified for the presence of tumor and specimens fixed in fixatives other than formalin are not acceptable. Samples <10% tumor burden will not be tested, as false negative results cannot be ruled out. Surgical pathology report should be included. Acid decalcification compromises the specimen quality and is not acceptable. Improperly labelled specimens will be rejected (must have two patient identifiers); frozen blood or bone marrow; FFPE blocks. PB and BM specimens collected in containers other than EDTA and NaHep; specimens >7 days old;

5 days for original heme samples; 10 years FFPE

Clinical indication and specimen source is required for the assay.