KIT

KIT Full Name

v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

KIT Introduction

KIT gene encodes CD117 which functions as a receptor tyrosine kinase that binds stem cell factor (SCF) to activate the proto-oncogene located at chromosome 4q12. The binding of ligand to KIT triggers dimerization and autophosphorylation events which activate multiple signaling pathways including PI3K/AKT and MAPK/ERK and JAK/STAT and SRC to control cell survival and proliferation and migration and apoptosis resistance. The biological function of KIT includes maintaining hematopoietic stem cells and their development and melanocyte formation and pigmentation and survival of primordial germ cells and mast cell expansion and activation and gastrointestinal movement through interstitial cells of Cajal.

Figure 1. Mast cell cKIT (CD117) receptor structure.(Source: Gilreath JA, et al. 2019)

Due to its involvement in multiple developmental and homeostatic processes, dysregulation of KIT can result in a variety of non-malignant disorders. The loss of function or decreased activity in KIT leads to multiple disorders which include impaired blood cell production and infertility and piebaldism and gastrointestinal motility problems. The continuous activation of KIT leads to uncontrolled mast cell growth and activation which results in allergic diseases and mast cell disorders.

The development of tumors occurs through KIT signaling abnormalities which result from mutations and overexpression and ligand-independent activation. The juxtamembrane region of KIT contains the most common mutations which occur in exon 11 of gastrointestinal stromal tumors (GISTs) and less frequently in exons 9, 13 and 17. The D816V mutation along with other KIT alterations appear in various cancers including acute myeloid leukemia and systemic mastocytosis and melanoma and seminoma. The discovery of KIT mutations has made it a crucial therapeutic target which resulted in the creation of tyrosine kinase inhibitors including imatinib and sunitinib and regorafenib and avapritinib. The selection of treatment depends on the specific mutation present in the patient.

Alternate Names for KIT

KIT; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; PBT; SCFR; C-Kit; CD117; mast/stem cell growth factor receptor Kit; p145 c-kit; proto-oncogene c-Kit; piebald trait protein

• Immunohistochemistry Antibodies for Pathology

• 1.Gilreath JA, et al. Novel approaches to treating advanced systemic mastocytosis. Clin Pharmacol . 2019, 11:77-92.