The Human Endometrial Cancer qBiomarker Somatic Mutation PCR Array is a translational research tool that allows rapid, accurate, and comprehensive profiling of the somatic mutations in human endometrial cancer samples in the following key genes: AKT1, BRAF, CTNNB1/beta-catenin, FBXW7, FGFR2, HRAS, KRAS, PIK3CA, PTEN, and P53. These mutations warrant extensive investigation to enhance the understanding of carcinogenesis and identify potential drug targets. Numerous research studies have demonstrated the utility of individual and multiple somatic mutation status information in identifying key signaling transduction disruptions. For example, the mutation status of the EGFR and KRAS genes can predict the physiological response to certain drugs targeting these molecules. The Human Endometrial Cancer qBiomarker Somatic Mutation PCR Array, with its comprehensive content coverage, is designed for studying mutations in the context of endometrial cancer and has the potential for discovery and development of effective biomarkers for this cancer type and other cancer types in which these mutations were identified. This array includes 84 DNA sequence mutation assays designed to detect the most frequent, functionally verified, and biologically significant mutations in human endometrial cancer. These mutations were chosen from curated, comprehensive somatic mutation databases and peer-reviewed scientific literature, and represent the most frequently recurring somatic mutations compiled from over 1700 endometrial cancer samples. The simplicity of the product format and operating procedure enables routine somatic mutation profiling in any research laboratory with access to real-time PCR instruments.
AKT1: 1 Assay
The mutation assay detects the best known AKT1 mutation, c.49G>A, p.E17K. This is a PH domain mutation that results in constitutive targeting of AKT1 to plasma membrane.
BRAF: 2 Assays
There are two major classes of BRAF mutations. One class leads to increased BRAF kinase activity, such as the p. V600E mutation. The other class leads to impaired kinase activity, such as the p.G469A mutation.
CTNNB1: 20 Assays
The most frequently detected CTNNB1/beta-catenin mutations result in abnormal signaling in the WNT signaling pathway. The mutated codons are mainly several serine/threonine residues targeted for phosphorylation by GSK-3beta.
FBXW7: 1 Assay
Typically detected mutations lay in either the third or fourth repeat of the protein's WD40 domain, typically involved in protein-protein interactions.
FGFR2: 2 Assays
The most frequently identified mutations occur in the kinase domain and non-kinase extracellular domains such as the hinge region and IgG-like domain. Some of the somatic mutations also correspond to congenital SNPs involved in genetic diseases.
HRAS: 1 Assay
The most important HRAS mutation in endometrial cancers occurs at codon 61.
KRAS: 10 Assays
The mutation assays include the most frequently occurring mutations in KRAS codons 12, 13, and 61. Mutations at these positions result in reduced intrinsic GTPase activity and/or cause KRAS to become unresponsive to RasGAP.
PIK3CA: 16 Assays
The most frequently occurring PIK3CA mutations mainly belong to two classes: gain-of-function kinase domain activating mutations and helical domain mutations that mimic activation by growth factors.
PTEN: 27 Assays
The most commonly detected PTEN loss-of-function mutations are due to either truncation (p.R233* and p.R130*) or point mutations causing phosphatase inactivation (p.R130 and p.R173 mutations).
TP53: 4 Assays
The most frequently detected somatic mutations in TP53 are largely composed of DNA-binding domain mutations which disrupt either DNA binding or protein structure.