Capture-based next-generation sequencing reveals multiple actionable mutations in cancer patients failed in...

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Targeted cancer therapies, including monoclonal antibodies and small molecule inhibitors, have advanced treatment over the last decade.
• These therapies offer tumor specificity and reduced side effects compared to traditional treatments.
• Next-generation sequencing (NGS) is emerging as a key diagnostic tool for personalized cancer therapy due to its accuracy, sensitivity, and high throughput.

Purpose of the Study:

• To develop and validate a next-generation sequencing (NGS)-based cancer genomic diagnostic method.
• To assess the clinical applicability of NGS for identifying actionable mutations in various cancer types.

Main Methods:

• Development and validation of an NGS-based assay targeting 115 clinically relevant genes.
• Analysis of diverse specimen types (blood, tumor tissue, body fluid) from 10 cancer patients.
• Utilization of in-house developed, clinically applicable analytical pipelines for sequencing data analysis.

Main Results:

• Assessment of analytical sensitivity, specificity, and accuracy of the NGS diagnostic method.
• Detection of base substitutions, insertions/deletions (indels), and gene copy number variations (CNVs) using the developed pipelines.
• Identification of actionable mutations (e.g., EGFR, PIK3CA, TP53, KRAS) in lung cancer cases, indicating drug susceptibility and resistance.

Conclusions:

• NGS-based molecular diagnosis demonstrates high sensitivity and comprehensiveness in detecting cancer genomic alterations.
• The validated NGS approach supports direct clinical application for guiding personalized targeted therapy decisions.