Cutaneous mastocytosis; Urticaria pigmentosa (Cutaneous mastocytosis) - Gen KIT

Mastocytosis is a morphologic diagnosis and can not be diagnosed only by clinical findings. Actually it is a clonal disease progenitors of hematopoietic cells of the bone marrow, manifesting a wide spectrum of clinical and morphological presentations. Mastocytosis is classified into four groups, with some variations in some of them: a) cutaneous mastocytosis (urticaria pigmentosa); b) Systemic mastocytosis; c) mast cell sarcoma; d) extracutaneous mastocytoma.

They have proposed two kinds of criteria for diagnosis of mastocytosis: major criterion and minor criteria. The most valid criterion alone for diagnosis, tissue infiltration is focal and compact mast. Minor criteria that would not be separately sufficient for diagnosis would be: 1) the presence of mast cells spicular; 2) immunophenotype atypical mast cells expressing the CD25 marker; 3) presence of point mutation activating kit at codon 816 (KIT D816V); and 4) elevated serum tryptase (> 20 ng / ml). The major criterion, and two of the four minor criteria (1 and 2), are morphological criteria. The major criterion is isolated diagnosis of mastocytosis. With minor criteria would be needed three of them for diagnosis.

The KIT gene (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog), also named CD117, C-Kit, PBT or SCFR gene is located on the long arm of chromosome 4 (4q12). This gene is a proto - oncogene encoding the KIT protein, which is a transmembrane receptor for stem cell factor (SCF: Stem Cell Factor) intrinsic tyrosine kinases and is essential for normal development of stem cells. Binding of KIT protein with the active stem cell factor protein, which in turn activates other proteins within the cell by adding a phosphate group in specific positions. This process, called phosphorylation results in the activation of a number of proteins in multiple signaling pathways. Constitutive activation of the signaling pathway SCF / KIT is associated with cell proliferation, maturation and differentiation, suppression of apoptosis, degranulation and modification in the properties of adhesion and motility of activated cells. Specifically, signaling the KIT protein is important for the development of certain types of cells, including germ cells, hematopoietic stem cells, mast cells, interstitial cells of Cajal (ICC), and melanocytes.

Mutations in the KIT gene cause constitutive activation of the receptor kinase that this gene encodes (KIT). That is, dysregulation of receptor activation, activated independently ligand binding occurs, which causes excessive growth and accumulation of mast cells. Mastocytosis causing mutations occur in a majority (> 90%) in exon 17 of the KIT gene, but they have also found occasionally in exons 8, 9, 10 and 11. In 93% of cases the mutation responsible is located at codon 816 (D816V). This substitution provides resistance to imatinib, used as a growth inhibitor of mastocíticas cells because it causes certain structural changes in the kinase domain prevent binding of imatinib. Thus, the vast majority of patients with mastocytosis can not benefit from treatment with imatinib to be carriers of the mutation D816V. Such cases agree be detected to proceed with treatment.

Tests in IVAMI: in IVAMI perform detection of mutations associated with mastocytosis, by complete PCR amplification of the exons of the KIT gene, and subsequent sequencing. It is recommended to begin the study of exon 17, which are located more than 90% of mutations associated with mastocytosis and, if not found, continue detection exons 8, 9, 10 and 11. Listen

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).