Gen EGFR

EGFR (Epidermal Growth Factor Receptor), synonymously also known as ERBB (ERythroBlastic leukemia); ERBB1; HER1 (Human Epidermal growth factor Receptor), is a transmembrane receptor. Its activation by binding the ligand triggers intracelular signaling cascade which effects the gene expression and leads to cell proliferation. Possible dysregulation of this signaling pathway can therefore lead to tumor progression.

The occurence of mutations in this gene is associated with lung carcinoma. Predictive investigation of activation mutations EGFR are performed in patients with NSCLC after the determination of morphologic diagnosis. The incidence of mutations correlates with the efficiency of the effect of gefitinib (Iressa) and erlotinib (Tarceva) tyrosine kinase inhibitors.

Examination

We perform the examination of the EGFR gene with a focus on the detection of mutations in exons 18, 19, 20 and 21. We use PCR and reverse hybridisation using EGFR XL StripAssay (ViennaLab) kit.

Analytical sensitivity and specificity of the sequencing: 99%.

Limitations:

Mutations deep in the introns and regulatory sequences are not detected. Rare polymorphisms in the location of primers and probes annealing may cause a diagnostic error.

In the case of the analysis of somatic mutations by sequencing the mutations will not be detected, if the altered cell line is not represented by at least 20%, in the case of analysis by reverse hybridization - 1%, in the case of analysis by real-time PCR - 5%.

References

  1. Pesek M, Benesova L, Belsanova B, Mukensnabl P, Bruha F, Minarik M.: Dominance of EGFR and insignificant KRAS mutations in prediction of tyrosine-kinase therapy for NSCLC patients stratified by tumor subtype and smoking status. Anticancer Res. 2009 Jul;29(7):2767-73.
  2. Luping Lin and Trever G. Bivona: Mechanisms of Resistance to Epidermal Growth Factor Receptor Inhibitors and Novel Therapeutic Strategies to Overcome Resistance in NSCLC Patients. Chemotherapy Research and Practice Volume 2012 (2012), Article ID 817297, 9 pages doi:10.1155/2012/817297.