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ErbB2/HER2/neu Pathway Mutation PCR Array

Human
 
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.

 

Assay Functional Annotations How It Works References Resources
 
Modify this Array   
ERBB2/HER2/neu gene:
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 domain region.

AKT gene:
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.

BRAF gene:
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 p.G469A mutations.

KRAS gene:
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.

HRAS gene:
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.

NRAS gene:
12 NRAS mutation assays are included on the panel to cover codon positions 12, 13, and 61, as well as mutation p.A18T.

MEK1 gene:
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.

PTEN gene:
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 mutations).

 

Assay Functional Annotations How It Works References Resources
 

Overview of the qBiomarker Somatic Mutation PCR Array / Assay Protocol

Overview of the qBiomarker Somatic Mutation PCR Array / Assay Protocol.
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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Assay Functional Annotations How It Works References Resources
 
  1. 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.

  2. The PKB/AKT pathway in cancer.Carnero A. Curr Pharm Des. 2010 Jan; 16(1):34-44.

  3. BRAF, a target in melanoma: implications for solid tumor drug development.
    Flaherty KT, McArthur G. Cancer. 2010 Jul 13. [Epub ahead of print].

  4. Clinical relevance of KRAS in human cancers. Jancík S, Drábek J, Radzioch D, Hajdúch M.
    J Biomed Biotechnol. 2010; 2010:150960.

  5. Oncogenic Ras in tumour progression and metastasis. Giehl K. Biol Chem. 2005 Mar; 386(3):193-205.

  6. 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; 106(48):20411-6.

  7. 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.

  8. Oncogenic mutations as predictive factors in colorectal cancer. Ličvre A, Blons H, Laurent-Puig P. Oncogene. 2010 May 27; 29(21):3033-43.

  9. PI(3)King Apart PTEN's Role in Cancer. Zhang S, Yu D. Clin Cancer Res. 2010 Jul 8. [Epub ahead of print].

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Assay Functional Annotations How It Works References Resources
 

User Manual qBiomarker Somatic Mutation PCR Array System (PDF)
Data Analysis qBiomarker Somatic Mutation PCR Array Data Analysis Software
Application Data Detection Limits, Cancer Pathways
FAQ Frequently Asked Questions about Somatic Mutation Assays and Arrays
Webinar qBiomarker Somatic Mutation Analysis: Real-World Application Data
Slide Presentation> Presentation about qBiomarker Somatic Mutation Assays and Arrays (PDF)
Scientific Poster A Novel Tool for Pathway-Focused Cancer Mutation Profiling (PDF)
Presented at American Association for Cancer Research 2011
White Paper Rapid and accurate cancer somatic mutation profiling with the qBiomarker Somatic Mutation PCR Array (PDF)
Product Profile For screening biology-focused panels of gene mutations (PDF)

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