A receptor tyrosine kinase proto-oncogene that can acquire oncogenic activity through mutation or rearrangement.
The RET receptor tyrosine kinase plays a crucial role in cell growth and differentiation.
RET fusions create a protein that is overexpressed on the surface of cancer cells.
Changes by RET nutations result in ligand independent signaling and oncogenic enesis.
RET is constantly sending signals into the cell to grow and develop.
There are several RET-fusion mutations.
The most common mutation is KIF5B, and others are NCOA4, CCDC6, TRIM33.
KIF5B is the most common, between 70% and 90% of cases.
RET fusions act in the process of oncogenesis.
RET rearrangements are observed in 1-2% of non-small cell lung cancers and in 60% of sporadic cases of medullary thyroid cancer and 90% of hereditary medullary thyroid cancer.
Mutations in RET, a transmembrane proto-oncogene located on chromosome 10q11.2, are responsible for MEN2.
The protein produced by RET is critical during embryonic development of the enteric nervous system and kidneys.
RET consists of 3 domains, including a cysteine-rich extracellular receptor domain, a hydrophobic transmembrane domain, and an intracellular tyrosine kinase catalytic domain.
RET germline mutations are present in virtually all patients with MEN2A and MEN2B, and somatic RET mutations are present in approximately 50% of sporadic MTCs.
In sporadic MTC that is RET mutation–negative, mutations in genes involving the RAS pathway—HRAS, KRAS, or (rarely) NRAS—are often found.
RET mutations are associated with more aggressive type medullary thyroid cancer.
RET mutations are also observed in papillary renal cell carcinoma, breast, colon and pancreatic cancers.
RET mutations are associated with a high risk of brain metastases in non-small cell lung cancer.
A single-pass transmembrane receptor tyrosine kinase that is vital for the normal development of several tissues in cell types, particularly of neural and genitourinary tissues and for homeostasis.
Implicated as a driver of several tumor types.
Normally expressed on neurons, sympathetic and parasympathetic ganglia, testis germ cells, urogenital tract cells, adrenal medullary cells, and thyroid C cells.
RET ligands are members of the glial cells derived neurotrophic factor family, and ligand binding results in RET auto phosphorylation and activation downstream cellular alliteration, cell migration and differentiation pathways including: RAS/MAPK/ERK, PI3K/AKT, and phospholipase C-gamma
Loss of function mutation was associated with Hirschsprung disease.
Gain of function mutations are associated with malignancies including non-small cell lung cancer, and medullary thyroid carcinoma.
RET activating point mutations are commonly found in medullary thyroid cancer, amounting to more than 60% of such cases.
RET gene rearrangement found in more than 10% of papillary thyroid tumors, 1-2% of non-small cell lung cancers, and one percent of breast, Colorectal, pancreatic, and esophageal cancers.
RET Has been identified as a driver in some melanoma and chronic myelomonocytic leukemias.