FGFR Pathway Mutation PCR Array

The fibroblast growth factor receptors (FGFRs) are receptors that bind fibroblast growth factors (FGFs), members of the largest family of growth factor ligands. The FGFRs and their downstream signaling cascades have been implicated in a diverse range of cellular processes including proliferation, apoptosis, survival, chemotaxis, cell adhesion, and differentiation. The importance of proper FGFR signaling is evident from genetic studies in human and mouse models demonstrating disruption of FGF signaling by mutations cause a variety of disorders including skeletal diseases, infertility, and cancer.

The Human FGFR Pathway qBiomarker Somatic Mutation PCR Array is a translational research tool that allows rapid and accurate profiling of the somatic mutation status of FGFR genes and key genes in the FGFR signaling pathways: AKT, BRAF, KRAS, HRAS, NRAS, MEK1, PIK3CA, and PTEN. The utility of individual and multiple 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 FGFR Pathway qBiomarker Somatic Mutation PCR Array, with its comprehensive content coverage, is designed for studying mutations in the context of the FGFR pathway and has the potential for discovering drug target biomarkers for a variety of human diseases involving the FGFR signaling pathway and downstream effectors. This array covers 85 DNA sequence mutation assays designed to detect the most frequent, functionally verified, and biologically most significant mutations in the FGFR pathways. These mutations were chosen from curated, comprehensive somatic mutation databases and peerreviewed scientific literature. 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.

FGFR genes (FGFR1, FGFR2, FGFR3):
15 mutation assays are included for FGFR1, 2 and 3 in this panel. These assays detect the most frequently identified
kinase domain mutations and non-kinase domain (e.g. extracellular domains such as the hinge region and IgG-like
domain) mutations. Some of the somatic mutations included have congenital correlates that are involved in genetic
diseases.

AKT gene:
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 gene:
Two classes of mutation assays are included. One class covers mutations that lead to increased BRAF kinase
activity, such as the p.V600 mutations. The other class detects mutations that lead to impaired kinase activity, such
as the p.G464V, p.G466V, and p.G469A mutations.

KRAS gene:
16 KRAS mutation assays provide comprehensive analysis capacity for the most frequently occurring mutations in
KRAS codon positions 12, 13, and 61. Mutations at these positions result in reduced intrinsic GTPase activity and/or
cause KRAS to become unresponsive to RasGAP. The p.Q22K mutation assay is also included.

HRAS gene:
Similar to KRAS mutation assays, the 13 HRAS mutation assays on this panel aim to cover the most important
HRAS mutations identified in cancers at codon 12, 13, and 61 positions.

NRAS gene:
12 NRAS mutation assays are included on the panel to cover codon positions 12, 13, and 61.

MEK1 gene:
4 assays for mutations with significance in cancer were included on this panel. These mutations cluster in MEK1 Nterminal negative regulatory domain and an adjacent domain, and are all activating mutations (i.e. lead to upregulated intrinsic MEK1 kinase activity).

PIK3CA (phosphatidylinositol 3-kinase catalytic subunit) gene:
The mutation assays covered on this panel can detect 7 of the most frequently occurring PIK3CA mutations that
belong to two classes: p.H1047 mutations, which are activating, kinase domain mutations; and mutations in P539-
E545 region, which are helical domain mutations that mimic activation by growth factors.

PTEN gene:
Included on the panel are 6 most commonly detected PTEN loss-of-function mutations that are due to either
truncation (p.R233* and p.R130*) or point mutation-caused phosphatase inactivation (p.R130 and p.R173
mutations).