KIT D816 Mutation Analysis (Mastocytosis)
KIT D816 Mutation Analysis (Mastocytosis)
This test is used to diagnose systemic mastocytosis (SM) or mixed lineage hematopoietic neoplasms that have a mast cell component and to stratify prognosis of core-binding factor (CBF) acute myeloid leukemia (AML).
Test Summary
KIT D816 Mutation Analysis (Mastocytosis)
Test code: 91772
Clinical use
- Diagnose systemic mastocytosis (SM) or mixed lineage hematopoietic neoplasms that have a mast cell component
- Stratify prognosis of core-binding factor (CBF) acute myeloid leukemia (AML) with t(8;21) or inv(16)/t(16;16) chromosomal alterations
Clinical background
Mutations in the KIT oncogene lead to increased cell proliferation through activation of the KIT receptor tyrosine kinase. Knowledge of a person’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.2
Non–mast cell expansions in many SM-associated hematologic malignancies also contain KIT D816 mutations.1,3 The frequency of these mutations in a patient sample can be used in conjunction with mast cell counts to diagnose mixed lineage hematopoietic neoplasms.3 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.3
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.4
KIT D816 mutations also occur in up to 30% of patients with CBF AML,5 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(8;21) or inv(16)/t(16;16) chromosomal alterations is indicative of a worse prognosis.6 Identification of KIT mutations provides prognostic information that can be helpful when selecting CBF AML treatment strategies.6
Because mutated cells comprise only a fraction of cells within a patient sample, a sensitive detection method such as next-generation sequencing (NGS) is important for reliable mutation testing. Furthermore, NGS can detect less common codon 816 variants such as D816Y and D816H.
Individuals suitable for testing
- Patients with suspected or established SM or related hematologic malignancies
- Patients with AML who have t(8;21) or inv(16)/t(16;16) chromosomal alterations
For patients with gastrointestinal stromal tumor (GIST) or melanoma, use test code 19961, which provides NGS analysis of KIT regions relevant to these conditions (ie, exons 2, 3, 8, 9, 10, 11, 13, 14, 17, 18, and 19).
Method
- NGS to detect mutations at codon 816 of the KIT gene
- Analytical sensitivity: detects mutant alleles that constitute ≥2% of alleles present in test sample
- Results reported: presence or absence of KIT mutation at codon 816; details of the mutation detected and the percentage of mutant alleles in the sample
Interpretive information
Presence of an activating KIT D816 mutation is consistent with a diagnosis of SM in patients with compatible morphologic and clinical findings.2 If the percentage of mutant KIT alleles is much greater than the percentage of mast cells in a sample, a non–mast cell neoplasm may be present.3 Mast cell counts are not included in this test.
Presence of the KIT D816V mutation is associated with a lack of response to imatinib therapy in patients with aggressive SM.4
In patients with CBF AML, presence of a KIT D816 mutation indicates worse prognosis.6
References
- Garcia-Montero AC, Jara-Acevedo M, Teodosio C, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108(7):2366-2372. doi:10.1182/blood-2006-04-015545
- Gotlib J, Pardanani A, Akin C, et al. International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013;121(13):2393-2401. doi:10.1182/blood-2012-09-458521
- Zhao W, Bueso-Ramos CE, Verstovsek S, et al. Quantitative profiling of codon 816 KIT mutations can aid in the classification of systemic mast cell disease. Leukemia. 2007;21(7):1574-1576. doi:10.1038/sj.leu.2404680
- Gleevec®. Prescribing information. Novartis Pharmaceuticals Corporation; 2024.
- Duployez N, Marceau-Renaut A, Boissel N, et al. Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood. 2016;127(20):2451-2459.
doi:10.1182/blood-2015-12-688705 - National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Acute myeloid leukemia. Version 2.2025. Published January 27, 2025. https://www.nccn.org
Content reviewed 4/2025
This test is used to diagnose systemic mastocytosis (SM) or mixed lineage hematopoietic neoplasms that have a mast cell component and to stratify prognosis of core-binding factor (CBF) acute myeloid leukemia (AML).
Test Summary
KIT D816 Mutation Analysis (Mastocytosis)
Test code: 91772
Clinical use
- Diagnose systemic mastocytosis (SM) or mixed lineage hematopoietic neoplasms that have a mast cell component
- Stratify prognosis of core-binding factor (CBF) acute myeloid leukemia (AML) with t(8;21) or inv(16)/t(16;16) chromosomal alterations
Clinical background
Mutations in the KIT oncogene lead to increased cell proliferation through activation of the KIT receptor tyrosine kinase. Knowledge of a person’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.2
Non–mast cell expansions in many SM-associated hematologic malignancies also contain KIT D816 mutations.1,3 The frequency of these mutations in a patient sample can be used in conjunction with mast cell counts to diagnose mixed lineage hematopoietic neoplasms.3 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.3
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.4
KIT D816 mutations also occur in up to 30% of patients with CBF AML,5 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(8;21) or inv(16)/t(16;16) chromosomal alterations is indicative of a worse prognosis.6 Identification of KIT mutations provides prognostic information that can be helpful when selecting CBF AML treatment strategies.6
Because mutated cells comprise only a fraction of cells within a patient sample, a sensitive detection method such as next-generation sequencing (NGS) is important for reliable mutation testing. Furthermore, NGS can detect less common codon 816 variants such as D816Y and D816H.
Individuals suitable for testing
- Patients with suspected or established SM or related hematologic malignancies
- Patients with AML who have t(8;21) or inv(16)/t(16;16) chromosomal alterations
For patients with gastrointestinal stromal tumor (GIST) or melanoma, use test code 19961, which provides NGS analysis of KIT regions relevant to these conditions (ie, exons 2, 3, 8, 9, 10, 11, 13, 14, 17, 18, and 19).
Method
- NGS to detect mutations at codon 816 of the KIT gene
- Analytical sensitivity: detects mutant alleles that constitute ≥2% of alleles present in test sample
- Results reported: presence or absence of KIT mutation at codon 816; details of the mutation detected and the percentage of mutant alleles in the sample
Interpretive information
Presence of an activating KIT D816 mutation is consistent with a diagnosis of SM in patients with compatible morphologic and clinical findings.2 If the percentage of mutant KIT alleles is much greater than the percentage of mast cells in a sample, a non–mast cell neoplasm may be present.3 Mast cell counts are not included in this test.
Presence of the KIT D816V mutation is associated with a lack of response to imatinib therapy in patients with aggressive SM.4
In patients with CBF AML, presence of a KIT D816 mutation indicates worse prognosis.6
References
- Garcia-Montero AC, Jara-Acevedo M, Teodosio C, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108(7):2366-2372. doi:10.1182/blood-2006-04-015545
- Gotlib J, Pardanani A, Akin C, et al. International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood. 2013;121(13):2393-2401. doi:10.1182/blood-2012-09-458521
- Zhao W, Bueso-Ramos CE, Verstovsek S, et al. Quantitative profiling of codon 816 KIT mutations can aid in the classification of systemic mast cell disease. Leukemia. 2007;21(7):1574-1576. doi:10.1038/sj.leu.2404680
- Gleevec®. Prescribing information. Novartis Pharmaceuticals Corporation; 2024.
- Duployez N, Marceau-Renaut A, Boissel N, et al. Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood. 2016;127(20):2451-2459.
doi:10.1182/blood-2015-12-688705 - National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Acute myeloid leukemia. Version 2.2025. Published January 27, 2025. https://www.nccn.org
Content reviewed 4/2025