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KIT D816 Mutation Analysis (Mastocytosis)

KIT D816 Mutation Analysis, (Mastocytosis)

Test Summary

KIT D816 Mutation Analysis (Mastocytosis)


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,5,6 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.7 According to the National Comprehensive Cancer Network (NCCN) and European LeukemiaNet guidelines, identification of KIT mutations provides prognostic information that can be helpful when selecting CBF AML treatment strategies.7,8

Because mutated cells comprise only a fraction of cells within a patient sample, a sensitive detection method such as pyrosequencing is important for reliable mutation testing.3 Furthermore, pyrosequencing 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 KIT gene sequencing of regions relevant to these conditions (ie, exons 8, 9, 11, 13, and 17).


  • PCR-based pyrosequencing of 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; the percentage of mutant alleles in the sample is also reported

Reference Range

No mutation detected

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.7


  1. 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;108:2366-2372.

  2. 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;121:2393-2401.

  3. 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;21:1574-1576.

  4. Gleevec® (imatinib mesylate) [package insert]. East Hanover, NJ: Novartis; 2013.

  5. Cairoli R, Beghini A, Grillo G, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood. 2006;107:3463-3468.

  6. Paschka P, Marcucci G, Ruppert AS, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol. 2006;24:3904-3911.

  7. NCCN Clinical Practice Guidelines in Oncology™. Acute myeloid leukemia. V 2.2013. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed October 16, 2013.

  8. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453-474.

This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. Performance characteristics refer to the analytical performance of the test.

 Content reviewed 12/2013

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