Epidermal growth factor receptor mutation testing: From conventional to real-time diagnosis of lung cancer

Abstract

Patients with non-small cell lung cancer (NSCLC) commonly harbor epidermal growth factor receptor (EGFR) mutation. Due to the complex disease pathology, early-stage diagnosis of patients with EGFR mutation is essential to make appropriate treatment decision. Tyrosine kinase inhibitors (TKIs) are commonly used for their treatment, but almost half of the patients with EGFR mutation do not respond to the available TKIs and develop acquired resistance owing to T790M mutation. The presence of T790M mutation also warrants a robust diagnostic method so as to allow clinicians to modify cancer treatment. Numerous diagnostic techniques for the detection of EGFR mutation, however, their performance and working profile variation necessitate a comparative evaluation for the selection of a better diagnostic method or an advanced combination of theirs. The present review compares various EGFR-mutation detection techniques such as Sanger sequencing, next-generation sequencing, and different polymerase chain reaction (PCR)-based methods. It also highlights the role of advanced PCR-based techniques, i.e., real-time or quantitative PCR and digital droplet PCR (ddPCR) for detecting EGFR mutations in NSCLC patients. ddPCR, when compared to other methods, shows enhanced sensitivity, superior reliability, and improved time and cost-effectiveness. Moreover, its ability to detect EGFR mutations including T790M, in both conventional (solid tissue biopsy samples) and nonconventional sample sources (blood, plasma, and urine samples), gives it an edge over other diagnostic techniques and support its integration in clinical practice setting.

Keywords: Digital droplet polymerase chain reaction; Sanger sequencing; T790M mutation; epidermal growth factor receptor; next-generation sequencing; quantitative polymerase chain reaction.