The Human Skin Cancer qBiomarker Somatic Mutation PCR Array is a translational research tool that allows rapid, accurate and comprehensive profiling of the top somatic mutations in human skin cancer samples in the following genes: BRAF, CDKN2A, CTNNB1/beta-catenin, FGFR3, GNAQ, HRAS, KIT, KRAS, NRAS, PIK3CA, PTCH1, PTEN, RB1, SMO, LKB1/STK11, 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 Skin Cancer qBiomarker Somatic Mutation PCR Array, with its comprehensive content coverage, is designed for the study of mutations in the context of skin cancer and has the potential for discovery and verification of drug target biomarkers for skin cancer types and other cancer types in which these mutations have been identified. This array includes 78 DNA sequence mutation assays designed to detect the most frequent, functionally verified, and biologically significant mutations in human skin cancers. 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 7100 skin cancer samples. The simplicity of the product format and operating procedure allows routine somatic mutation profiling in any research laboratory with access to real-time PCR instruments.
BRAF: 7 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.
CDKN2A: 7 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.
CTNNB1: 8 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.
FGFR3: 6 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.
GNAQ: 3 Assays
The mutations queried by these assays all lie in the protein's GTP nucleotide binding domain.
HRAS: 8 Assays
The mutation assays include the most important HRAS mutations identified in cancers at codons 12, 13, and 61.
KIT: 2 Assays
The most frequently identified KIT gain-of-function mutations include the D816V point mutation, the exon 11 (juxtamembrane domain) deletion and point mutations, an exon 9 insertion mutation, and exon 13 point mutations.
KRAS: 3 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.
NRAS: 11 Assays
The mutation assays include the most important NRAS mutations at codons 12, 13, and 61.
PIK3CA: 3 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: 3 Assays
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.
PTEN: 1 Assay
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).
RB1: 1 Assay
The highly recurrent RB loss of tumor suppressor function mutations are either due to truncation or disruption of binding partner interactions.
SMO: 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.
STK11: 1 Assay
The most commonly detected STK11/LKB1 inactivation mutations are mainly due to truncation or point mutations.
TP53: 13 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.