PDGFRA- 3 Exons Sequencing Test Cost & Procedure

Exons 3 of PDGFRA

The platelet-derived growth factor receptor alpha (PDFRA) gene and gastrointestinal cancers can both be found using sequencing tests. PCR and gene sequencing are used to identify any mutations in the PDGFRA gene before tumor existence is determined.

The chromosomal location of PDGFRA and KIT is 4q12, and both proteins have highly homologous protein structures made up of a number of domains, each of which plays a particular part in tyrosine kinase activation.

PDGFRA can bind to and be activated by a number of platelet-derived growth factor (PDGF) isoforms. Similar to how activated KIT initiates the JAK-STAT3, PI3K-AKT-mTOR, and RAS-MAPK pathways, which are crucial in controlling essential cellular processes including proliferation and death, so does activated PDGFRA.

The most prevalent type of digestive tract mesenchymal tumors are called gastrointestinal stromal tumors (GISTs), and 82–87% of them are characterized by the presence of PDGFRA and KIT gain-of-function mutations that are mutually exclusive. The second most often mutated oncogene in GISTs, after KIT, is PDGFRA.

Gain-of-function mutations cause PDGFRA and its downstream pathways to be constitutively activated in the absence of ligands, which ultimately promotes cell proliferation and prevents apoptosis. Awareness of the biology and antidote of GIST has been fundamentally altered by the designation of triggering modifications in the KIT and PDGFRA tyrosine kinase receptors and their position in the etiology of this illness.

PDGFRA mutations in GIST

Since most PDGFRA-mutated GISTs exhibit benign clinical characteristics, there is likely a low representation of these GISTs in clinical trials. The commonness of PDGFRA modifications varies, varying from two to fourteen percent  of GISTs. Most PDGFRA-mutated GISTs are gastrointestinal in origin and have mixed epithelioid and spindle histology or epithelioid shape.

Exons 12 and 18 seem to have the most primary PDGFRA mutations, with exon 14 being less frequently affected. Approximately 6% of GISTs carry exon 18 PDGFRA modifications, which are supposed to abnormally stabilize the kinase activation coil. Up to 75% of all PDGFRA-mutated tumors have an exon 18 D842V change, the most common mutation. The second most frequent type of PDGFRA mutation, affecting exon 12 (the juxtamembrane domain), is found in about 1-2% of GISTs.

A mutation in the PDGFRA juxtamembrane domain, which is thought to mediate an autoinhibitory role, results in hyperactivation. Exon 14 mutations are uncommon and often cluster at codon 659. Though its role is less well understood, exon 14 proximity to exon 12 suggests that it may help the juxtamembrane domain's auto inhibitory activity. Exon 18 has been the site of secondary PDGFRA mutations, which are frequently linked to main mutations in the same gene