c-MET Pathway Mutation PCR Array
|qBiomarker Somatic Mutation PCR Array: Human c-MET Pathway
|c-MET (also known as MET, HGFR) is a membrane receptor essential for embryonic development and wound
healing. Hepatocyte growth factor (HGF) is the only known ligand of the c-MET receptor. c-MET is deregulated in
many types of human malignancies, including cancers of the kidneys, liver, stomach, breast, and brain. Abnormal
MET activation in cancer correlates with poor prognosis, where aberrantly active c-MET triggers tumor growth,
angiogenesis and metastasis. c-MET activation triggers several key downstream oncogenic pathways including the
Ras-MAPK, PI3K, STAT, beta-catenin, and Notch pathways.
The Human c-MET Pathway qBiomarker Somatic Mutation PCR Array is a translational research tool that allows
rapid and accurate profiling of the somatic mutation status of the c-MET gene and additional key genes in two major
c-MET downstream signaling pathways: the Ras-MAPK pathway and the PI3K pathway. 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 c-MET Pathway qBiomarker
Somatic Mutation PCR Array, with its comprehensive content coverage, is designed for studying mutations in the
context of the c-MET pathway and has the potential for discovering drug target biomarkers for a variety of human
cancers involving the c-MET signaling pathway and downstream effectors. This array covers 83 DNA sequence
mutation assays designed to detect the most frequent, functionally verified, and biologically most significant
mutations in the c-MET pathway. These mutations were chosen from curated, comprehensive somatic mutation
databases and peer-reviewed 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.
The qBiomarker Somatic Mutation PCR Arrays are intended for molecular biology applications. This product is not
intended for the diagnosis, prevention, or treatment of a disease.
| Modify this Array
The assays included in this panel detect the most frequently identified c-MET gain-of-function mutations, such as the
tyrosine kinase domain and juxtamembrane domain point mutations.
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.
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.G469A mutation.
12 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.
Similar to KRAS mutation assays, the 8 HRAS mutation assays on this panel aim to cover the most important HRAS
mutations identified in cancers at codon 12, 13, and 61 positions.
10 NRAS mutation assays are included on the panel to cover codon positions 12, 13, and 61.
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 6 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.
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
The 15 assays included in this panel detect the most frequently identified PTPN11 mutations, such as lesions
affecting residues located in or close to the N-terminal SH2 domain/PTP-interacting surface, and mutations that
affect residues that control substrate specificity.
Included on the panel are 6 most commonly detected VHL point mutations or truncation mutations that lead to loss of
tumor suppressor function of the VHL protein.
Overview of the qBiomarker Somatic
Mutation PCR Array / Assay Protocol
Overview of the qBiomarker Somatic Mutation PCR Array / Assay
The procedure involves DNA extraction (QIAGEN QIAamp DNA Mini Kit or FFPE Tissue
Kit is recommended), an optional amplification (QIAGEN REPLI-g kit or REPLI-g
UltraFast kit is recommended) step for DNA isolated from fresh samples, qPCR
detection on qBiomarker Somatic Mutation PCR Arrays or Assays, and data analysis
(using the qBiomarker Somatic Mutation Data Analysis Template). An optional DNA
sample QC step immediately before the detection array or assay setup allows the
user to qualify the DNA samples.
Principle of Mutant Discrimination with ARMS®
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