Next-Generation Sequencing — High-Throughput DNA Testing

Next-generation sequencing is a high-throughput diagnostic platform that determines the exact nucleotide sequence of millions of DNA or RNA molecules in parallel. In oncology, it is used to examine tumour samples or circulating tumour DNA for pathogenic alterations, including point mutations, insertions, deletions, copy-number variations, and structural rearrangements across hundreds of cancer-related genes.

By analysing broad gene panels, whole exomes, or entire genomes simultaneously, NGS provides a comprehensive overview of a tumour's unique genomic architecture. Pathologists compare tumour DNA sequences against standard reference genomes to identify clinically actionable variations, which informs diagnosis, clarifies prognosis, and identifies potential resistance mechanisms that might affect treatment response.

Cancer treatments are increasingly tailored to individual genetic alterations rather than tumour location alone. NGS can identify targetable alterations that standard tests might overlook, matching you with approved targeted medicines or suitable clinical trials. Furthermore, NGS can reveal whether a cancer carries inherited alterations, indicating whether your family members might benefit from genetic counselling. It also prevents the use of therapies unlikely to work, saving valuable time and reducing unnecessary side effects.

NGS is performed on tissue obtained from a standard surgical biopsy or tumour resection, usually preserved in paraffin wax blocks. When tissue is scarce or difficult to access safely, a liquid biopsy may be collected via a routine blood draw to sequence circulating tumour DNA. Results typically take two to four weeks to process, depending on the complexity of the gene panel examined.

NGS is widely employed across many malignancies, particularly non-small cell lung cancer, where multiple actionable targets exist, such as EGFR, ALK, and ROS1. It is also routinely used in colorectal cancer, ovarian cancer, breast cancer, prostate cancer, melanoma, and gastrointestinal stromal tumours. In rare cancers or cancers of unknown primary origin, NGS is frequently utilised to identify unexpected treatment targets when standard options are limited.

NGS results directly guide the selection of targeted therapies, such as tyrosine kinase inhibitors or PARP inhibitors, tailored to specific alterations. They also determine eligibility for immune checkpoint inhibitors by assessing biomarkers such as microsatellite instability (MSI) and tumour mutational burden (TMB). If mutations causing resistance to previous medicines are detected, the team can adjust therapies proactively.