ErbB2/HER2/neu Pathway Mutation PCR Array
|qBiomarker Somatic Mutation PCR Array: Human ErbB2/HER2/neu Pathway
|ERBB2 (also known as HER2 and neu) is a cell membrane surface-bound receptor
tyrosine kinase and is normally involved in signal transduction pathways leading
to cell growth and differentiation. ERBB2 is a member of the ERBB protein
family, more commonly known as the epidermal growth factor receptor family.
Recent studies show that ERBB2 kinase domain somatic mutations occur in common
human cancers, such as lung adenocarcinomas, breast, gastric, and colorectal
cancers, and suggest that alterations of ERBB2-mediated signaling pathways by
ERBB2 mutations alone, or together with downstream mediator mutations, may
contribute to the development of human cancers.
The Human ERBB2 Pathway qBiomarker Somatic Mutation PCR Array is a
translational research tool that allows rapid and accurate profiling of the
somatic mutation status for the ERBB2/HER2/neu gene and several key downstream
signaling genes, including the RAS-MAPK and PI3K signaling pathway components.
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 ERBB2/HER2/neu Pathway qBiomarker Somatic Mutation PCR Array,
with its comprehensive content coverage, is designed for studying mutations in
the context of the ERBB2 pathway and has the potential for discovering and
verifying drug target biomarkers for a variety of human cancers involving the
ERBB2 signaling pathway and downstream effectors. This array covers 85 DNA
sequence mutation assays designed to detect the most frequent, functionally
verified, and clinically significant mutations in the ERBB2 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.
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11 mutation assays are included in this panel to provide
comprehensive coverage for the most frequently identified ERBB2
activating mutations. These mutations cluster in the ERBB2 kinase
The mutation assays 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.L597 and p.V600 mutations. The other class detects mutations that
lead to impaired kinase activity, such as the p.G464V, p.G466V and
17 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.L19F and p.Q22K mutation assays are also included.
Similar to KRAS mutation assays, the 13 HRAS mutation assays on this
panel aim to comprehensively cover the most important HRAS mutations
identified in cancers at codon 12, 13, and 61 positions.
12 NRAS mutation assays are included on the panel to cover codon
positions 12, 13, and 61, as well as mutation p.A18T.
4 assays for mutations with verified clinical significance in cancer
were included on the panel. These mutations cluster in MEK1
N-terminal negative regulatory domain and an adjacent domain, and
are all activating mutations (i.e. lead to up-regulated intrinsic
MEK1 kinase activity).
PIK3CA (phosphatidylinositol 3-kinase catalytic subunit) gene:
The mutation assays covered on this panel can detect 8 of the most
frequently occurring PIK3CA mutations that belong to three classes:
p.H1047 mutations, which are activating, kinase domain mutations;
mutations in the P539-E545 region, which are helical domain
mutations that mimic activation by growth factors; and a p.N1068fs*4
early stop codon mutation which is caused by insertion.
Included on the panel are 10 of the most commonly detected PTEN
loss-of-function mutations that are due to either truncation
(p.K6fs*4, p.R130*, p.R130fs*4, p.R233*, p.P248fs*5, and p.V317fs*3)
or point mutation-caused phosphatase inactivation (p.R130 and p.R173
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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Update on HER-2 as a target for cancer therapy:
intracellular signaling pathways of ErbB2/HER-2 and family members. Olayioye
MA. Breast Cancer Res. 2001; 3(6):385-9.
The PKB/AKT pathway in cancer.Carnero A. Curr Pharm Des.
2010 Jan; 16(1):34-44.
BRAF, a target in melanoma: implications for solid tumor
Flaherty KT, McArthur G. Cancer. 2010 Jul 13. [Epub ahead of print].
Clinical relevance of KRAS in human cancers. Jancík S,
Drábek J, Radzioch D, Hajdúch M.
J Biomed Biotechnol. 2010; 2010:150960.
Oncogenic Ras in tumour progression and metastasis. Giehl K.
Biol Chem. 2005 Mar; 386(3):193-205.
MEK1 mutations confer resistance to MEK and B-RAF
inhibition. Emery CM, Vijayendran KG, Zipser MC, Sawyer AM, Niu L, Kim JJ,
Hatton C, Chopra R, Oberholzer PA, Karpova MB, MacConaill LE, Zhang J, Gray
NS, Sellers WR, Dummer R, Garraway LA. Proc Natl Acad Sci U S A. 2009 Dec 1;
PIK3CA mutations in human solid tumors: role in sensitivity
to various therapeutic approaches. Ligresti G, Militello L, Steelman LS,
Cavallaro A, Basile F, Nicoletti F, Stivala F, McCubrey JA, Libra M. Cell
Cycle. 2009 May 1; 8(9):1352-8.
Oncogenic mutations as predictive factors in colorectal
cancer. Ličvre A, Blons H, Laurent-Puig P. Oncogene. 2010 May 27;
PI(3)King Apart PTEN's Role in Cancer. Zhang S, Yu D. Clin
Cancer Res. 2010 Jul 8. [Epub ahead of print].