The Human Head and Neck Cancer qBiomarker Somatic Mutation PCR Array is a translational research tool that allows rapid, accurate, and comprehensive profiling of the somatic mutations in human head and neck cancer samples in the following key genes: BRAF, CDKN2A, EGFR, FGFR3, HRAS, KRAS, MET, NRAS, PIK3CA, PTCH1, and P53. These mutations warrant extensive investigation to enhance the understanding of carcinogenesis and identify potential drug targets. The utility of somatic mutation status information in identifying key signaling transduction disruptions has been demonstrated in numerous research studies. For example, the mutation status of the EGFR and KRAS genes can predict the physiological response to certain drugs targeting these molecules. The Human Head and Neck Cancer qBiomarker Somatic Mutation PCR Array, with its comprehensive content coverage, is designed for studying mutations in the context of head and neck cancer and has the potential for discovery and verification of drug target biomarkers for this cancer type and other cancer types in which these mutations have been identified. This array includes 83 DNA sequence mutation assays designed to detect the most frequent, functionally verified, and biologically significant mutations in human head and neck 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 3000 head and neck cancer samples. The simplicity of the product format and operating procedure allows routine somatic mutation profiling in any research laboratory with access to a real-time PCR instrument.
BRAF: 1 Assay
The most important BRAF mutation in head and neck cancers leads to increased kinase activity, the p. V600E mutation.
CDKN2A: 8 Assays
The top CDKN2A loss-of-function mutations occur in the consensus ankyrin domain, which leads to inability to form stable complexes with its targets.
EGFR: 3 Assays
The most frequently identified EGFR mutations include P-loop and activation loop point mutations, kinase domain deletions, and insertion mutations.
FGFR3: 1 Assay
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: 12 Assays
The mutation assays include the most important HRAS mutations identified in cancers at codons 12, 13, and 61.
KRAS: 9 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.
MET: 2 Assays
These assays detect the most frequently identified c-MET gain-of-function mutations, such as tyrosine kinase domain and juxtamembrane domain point mutations.
NRAS: 1 Assay
The most important NRAS mutations in head and neck cancers occur at codon 12.
PIK3CA: 6 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.
PTCH1: 1 Assay
Mutations in this gene constitutively activate the WNT signaling pathway and the GLI transcription factors increasing the expression of genes involved in tumor cell growth, differentiation, and proliferation.
TP53: 39 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.