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Unit Code 88802:
KIT Asp816Val Mutation Analysis, Qualitative PCR

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Useful For

Diagnosing systemic mastocytosis

Clinical Information

Systemic mastocytosis is a hematopoietic neoplasm that can be

included in the general category of chronic myeloproliferative

disorders (CMPDs). These neoplasms are characterized by

excessive proliferation of 1 or more myeloid lineages, with cells

filling the bone marrow and populating other hematopoietic sites.

In systemic mastocytosis, mast cell proliferation is the defining

feature, although other myeloid lineages and B-cells are frequently

part of the neoplastic clone.

 

Function-altering point mutations in KIT, a gene coding for a membrane

receptor tyrosine kinase, have been found in myeloid lineage cells

in the majority of systemic mastocytosis cases. The most common KIT

mutation is an adenine-to thymine base substitution (A->T) at nucleotide

position 2468, which results in an aspartic acid-to-valine change in the protein

(Asp816Val). Much less frequently, other mutations at this same location

are found and occasional cases with mutations at other locations have

also been reported. Mutations at the 816 codon are believed to alter the

protein such that it is in a constitutively activated state. The main

downstream effect of KIT activation is cell proliferation.

 

Detection of a mutation at the 816 codon is included as 1 of the minor

diagnostic criteria for systemic mastocytosis in the World Health

Organization (WHO) classification system for hematopoietic neoplasms

and is also of therapeutic relevance, as it confers resistance to imatinib,

a drug commonly used to treat CMPDs. It is now clear that individual

mast cell neoplasms are variable with respect to the number of cell

lineages containing the mutation; some having positivity only in mast

cells and others having positivity in additional myeloid and even

lymphoid lineages. The mutation has not been reported in normal tissues.

Reference Values

An interpretive report will be provided indicating the mutation status

as positive or negative.

Interpretation

The test will be interpreted as positive or negative for KIT Asp816Val.

Cautions

Some systemic mastocytosis cases may have the mutation only in

mast cells. Since these cells rarely circulate in blood and are difficult

to obtain in significant numbers from bone marrow aspirate specimens,

false-negative results may occur if neoplastic cells are present below

the sensitivity of the assay (fewer than 0.01% mutated alleles).

 

The test is qualitative only. Reliable quantitative results cannot be issued.

Clinical Reference

1.   Garcia-Montero A, 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;108-2366-232.

 

2.   Valent P, Akin C, Sperr WR, et al:  Diagnosis and treatment of

      systemic mastocytosis:  state of the art. Br J Haematol

      2003;122:695-717

 

3.   Jaffe ES, Harris NL, Stein H, et al:  World Health Organization

      Classification of Tumours. Pathology & Genetics. Tumours of

      the Haematopoietic and Lymphoid Tissues. 2001, pp 291-302

Key