Next-generation sequencing (NGS) is a laboratory technology that rapidly reads the genetic material (DNA and RNA) extracted from a patient’s tumor or blood sample. This technique has transformed cancer care by shifting the focus from treating cancer based only on its location to treating it based on its unique molecular blueprint. NGS provides a detailed, high-resolution view of the genetic alterations driving a specific cancer, which helps doctors select treatments designed to target those biological mechanisms. NGS has become widely accepted as a standard tool in oncology, providing the foundation for precision medicine.
How Next-Generation Sequencing Works
NGS dramatically increased the speed and scale of genetic analysis compared to previous methods, such as Sanger sequencing, which could only read one small fragment of DNA at a time. Its power lies in massive parallel sequencing, a process that involves breaking the tumor’s DNA or RNA into millions of tiny fragments. Each fragment is sequenced simultaneously in a highly automated process. Computer software aligns the resulting short reads against a reference human genome, allowing scientists to reconstruct the complete sequence and identify deviations. This high-throughput capability means hundreds of genes can be analyzed in a single test.
Identifying Tumor Characteristics
The goal of NGS in oncology is to understand the specific genetic malfunctions that cause a tumor to grow and spread. NGS detects various types of alterations, including single-nucleotide variants (SNVs), small insertions and deletions (indels), copy number variations (CNVs), and gene fusions. These alterations are collectively known as biomarkers, which serve as distinguishing molecular characteristics of the tumor. For instance, an SNV is a change in a single DNA building block, while a gene fusion occurs when two separate genes break and join together. Identifying these biomarkers is essential because they dictate the tumor’s behavior and its susceptibility to different therapies.
Different Types of NGS Testing
Next-generation sequencing is a versatile technology that can be applied with different scopes, depending on the clinical need. The two most common approaches utilized in cancer care are targeted panels and Comprehensive Genomic Profiling (CGP).
Targeted Panels
Targeted panels sequence a small, select group of genes, typically between 10 and 50, that are known to be frequently altered and “actionable” in specific cancer types. This focused approach provides rapid results for the most common biomarkers in a particular tumor.
Comprehensive Genomic Profiling (CGP)
CGP involves sequencing a much larger number of genes, often hundreds, or even the entire exome (all protein-coding genes). CGP maximizes the chance of finding less common or novel biomarkers, including genomic signatures like Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). CGP is particularly valuable for rare cancers or when a targeted panel fails to identify a treatable alteration.
Translating Results into Treatment Decisions
The identification of tumor characteristics through NGS directly informs treatment selection by highlighting “actionable” mutations—genetic changes for which a specific drug or therapy exists. For example, finding a BRAF V600E mutation or an EGFR mutation can immediately guide the oncologist toward a targeted therapy. Targeted drugs are designed to interfere with the function of the abnormal protein created by the mutation, often leading to a more effective treatment than traditional chemotherapy. NGS results also determine a patient’s eligibility for immunotherapies, as biomarkers like high TMB or MSI suggest a tumor is more likely to respond to immune checkpoint inhibitors. Interpreting the complex data often involves a multidisciplinary team known as a Molecular Tumor Board, which helps translate the unique molecular profile into a personalized treatment strategy.