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KIT (D816V) Mutation, Mastocytosis/AML, Quantitative ddPCR
Test Code14098
CPT Codes
81273
Preferred Specimen
5 mL whole blood collected in an EDTA (lavender-top) tube
Minimum Volume
3 mL whole blood • 1 mL bone marrow
Other Acceptable Specimens
3 mL bone marrow collected in a sodium heparin (green-top) tube
Instructions
Specimen viability decreases during transit. Send specimen to testing lab for viability determination. Do not freeze. Do not reject.
Transport Temperature
Room temperature
Specimen Stability
Room temperature: Preferred
Refrigerated: Acceptable
Frozen: Unacceptable
Refrigerated: Acceptable
Frozen: Unacceptable
Methodology
Digital Drop Polymerase Chain Reaction (ddPCR)
Setup Schedule
Set up: Wed; Report available: 6-8 days
Reference Range
See Laboratory Report
Clinical Significance
Mutations in the KIT oncogene led to increased cell proliferation through activation of the KIT receptor tyrosine kinase. Knowledge of a patient's KIT mutation status can help physicians diagnose SM, a disease characterized by abnormal mast cell proliferation and accumulation in various organs. The KIT D816V mutation is present in more than 90% of patients with SM1; thus, presence of the mutation is one of the World Health Organization's minor criteria for diagnosis [1].
Non-mast cell expansions in many SM-associated hematologic malignancies also contain KIT D816V mutations [2]. The frequency of these mutations in a patient sample can be used in conjunction with mast cell counts to diagnose mixed lineage hematopoietic neoplasms [2]. For example, if mutant alleles constitute 60% of KIT alleles in a sample but mast cells constitute only 2% of total cells, then the presence of a non-mast cell neoplasm would be indicated. Furthermore, this result would indicate a clonal relationship between 2 morphologically distinct neoplastic components [2].
Knowledge of a patient's KIT D816 mutation status can also help a physician select appropriate SM treatment. Tyrosine kinase inhibitors such as imatinib have been used for patients with aggressive SM. However, when such patients harbor the KIT D816V mutation, imatinib is not effective and is therefore contraindicated [3].
KIT D816 mutations also occur in up to 30% of patients with CBF AML, a subgroup of AML defined by the presence of chromosomal alterations that disrupt CBF genes. CBF AML is normally associated with a favorable outcome, but the detection of KIT mutations in patients with t(18;21) or inv(16)/t(16;16) chromosomal alterations is indicative of a worse prognosis. According to the National Comprehensive Cancer Network (NCCN) and European Leukemia Net guidelines, identification of KIT mutations provides prognostic information that can be helpful when selecting CBF AML treatment strategies. [4,5].
Because mutated cells comprise only a fraction of cells within a patient sample, a sensitive detection method such as droplet digital PCR is important for reliable mutation testing.
References
1. Valent, P; Akin, C; and Metcalfe DD (2017) Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood 129 (11): 1420-1427
2. Andreas Reiter, A., George, T; and Gotlib, J (2020) New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis. Blood 135 (16): 1365-1376
3. Mariana Castells. M and Akin C (2021) Finding the right Kit inhibitor for advanced systemic mastocytosis. Nature Medicine 27: 2081-2082
4. Dohner, H; Wei, A; Applebaum, F et al. (2022) Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 140(12): 1345-1377
5. NCCN Acute Myeloid Leukemia 2024
Non-mast cell expansions in many SM-associated hematologic malignancies also contain KIT D816V mutations [2]. The frequency of these mutations in a patient sample can be used in conjunction with mast cell counts to diagnose mixed lineage hematopoietic neoplasms [2]. For example, if mutant alleles constitute 60% of KIT alleles in a sample but mast cells constitute only 2% of total cells, then the presence of a non-mast cell neoplasm would be indicated. Furthermore, this result would indicate a clonal relationship between 2 morphologically distinct neoplastic components [2].
Knowledge of a patient's KIT D816 mutation status can also help a physician select appropriate SM treatment. Tyrosine kinase inhibitors such as imatinib have been used for patients with aggressive SM. However, when such patients harbor the KIT D816V mutation, imatinib is not effective and is therefore contraindicated [3].
KIT D816 mutations also occur in up to 30% of patients with CBF AML, a subgroup of AML defined by the presence of chromosomal alterations that disrupt CBF genes. CBF AML is normally associated with a favorable outcome, but the detection of KIT mutations in patients with t(18;21) or inv(16)/t(16;16) chromosomal alterations is indicative of a worse prognosis. According to the National Comprehensive Cancer Network (NCCN) and European Leukemia Net guidelines, identification of KIT mutations provides prognostic information that can be helpful when selecting CBF AML treatment strategies. [4,5].
Because mutated cells comprise only a fraction of cells within a patient sample, a sensitive detection method such as droplet digital PCR is important for reliable mutation testing.
References
1. Valent, P; Akin, C; and Metcalfe DD (2017) Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood 129 (11): 1420-1427
2. Andreas Reiter, A., George, T; and Gotlib, J (2020) New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis. Blood 135 (16): 1365-1376
3. Mariana Castells. M and Akin C (2021) Finding the right Kit inhibitor for advanced systemic mastocytosis. Nature Medicine 27: 2081-2082
4. Dohner, H; Wei, A; Applebaum, F et al. (2022) Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 140(12): 1345-1377
5. NCCN Acute Myeloid Leukemia 2024
