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Epidermal growth factor receptor mutation testing: From conventional to real-time diagnosis of lung cancer
1Department of Medical Oncology, Apollo Speciality Hospital, Chennai, Tamil Nadu, India.
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.
Insights
Early diagnosis of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is crucial. Digital droplet PCR (ddPCR) offers a highly sensitive and reliable method for detecting these mutations, including T790M, in various sample types.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) frequently presents with epidermal growth factor receptor (EGFR) mutations.
- Accurate early diagnosis of EGFR mutations is vital for effective treatment selection and management of acquired resistance, such as T790M.
- Current diagnostic methods for EGFR mutations vary in performance, necessitating comparative evaluations.
Purpose of the Study:
- To compare various techniques for detecting EGFR mutations in NSCLC patients.
- To evaluate the role of advanced Polymerase Chain Reaction (PCR)-based methods, including digital droplet PCR (ddPCR).
- To highlight the advantages of ddPCR in EGFR mutation detection.
Main Methods:
- Review and comparison of diagnostic techniques: Sanger sequencing, next-generation sequencing, and various PCR-based methods.
- Focus on advanced PCR techniques: real-time PCR and digital droplet PCR (ddPCR).
- Evaluation of sensitivity, reliability, cost-effectiveness, and sample type versatility.
Main Results:
- Digital droplet PCR (ddPCR) demonstrates enhanced sensitivity and superior reliability compared to other methods.
- ddPCR offers improved time and cost-effectiveness for EGFR mutation detection.
- ddPCR can detect EGFR mutations, including T790M, in both solid tissue and liquid biopsy samples (blood, plasma, urine).
Conclusions:
- ddPCR presents significant advantages for detecting EGFR mutations in NSCLC.
- Its high sensitivity, reliability, and ability to analyze diverse sample types support its clinical integration.
- ddPCR facilitates timely treatment modifications for NSCLC patients, especially those with T790M resistance mutations.
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