Targeted therapies are dramatically improving cancer treatment. Next-generation sequencing (NGS) assays that profile genetic mutations are critical to enable more precise diagnostics, treatment, and disease monitoring. Developing assays with accuracy, sensitivity, and reproducibility for clinical use requires reference material designed for modern, high-throughput genomic assays.
Rapid evolution of cancer diagnostics
Many cancers share a small number of common mutations, but rare cancer- and patient-specific mutations arise during disease progression and in response to many frontline treatments. NGS can test for a wide array of distinct biomarkers, and their performance must be rigorously validated. Choosing between a comprehensive NGS assay method or a more focused, targeted NGS panel can be challenging. No single assay suits all applications and cancer types . That said, there is a trend towards larger panels of so-called comprehensive genomic profiling which allows for multiple diseases as well as complex biomarkers to be surveyed with a single sequencing assay.
Immunotherapy using checkpoint inhibitors is a powerful way to unleash the immune system to fight cancers. Today, only a fraction of patients see significant benefits from this treatment. Efforts are underway to change that by developing better biomarkers to predict treatment response. Some of them, such as TMB or MSI, can be also assayed by comprehensive genomic profiling.
Assessing cancer mutations through liquid biopsy combines the potential for early detection, disease diagnosis, and treatment monitoring in a minimally invasive test. Following resection of a primary tumor, it can be challenging to repeatedly biopsy certain sites prone to cancer recurrence, such as the lungs. NGS-based liquid biopsy assays for routine cancer.
New NGS platforms provide options for sequencing blood-based samples at an extremely high depth of coverage, offering high sensitivity and specificity for actionable biomarkers. This allows for detection of mutations in a very small number of cancer cells present in a patient. As the cost of data collection continues to plummet, analysis of data is increasingly seen as a bottleneck. New methodologies, such as molecular barcoding and bioinformatics using AI tools, have improved the accuracy of liquid biopsy assays.
NGS assay validation & collaboration
The advances make validating assay performance on specific sample types necessary and drive demand for high-quality genomic reference materials. Contrived materials designed to simulate patient samples are critical tools for the development and validation of laboratory-developed tests (LDTs) which focus on actionable mutations found in tumor and blood derived samples. The genomic applications being developed today weren’t possible ten years ago. Here are just few examples of how Seraseq® reference materials help to realize the promise of precision oncology.
- Friends of Cancer Research established a TMB harmonization consortium to standardize and harmonize TMB measurements across different NGS assays. The study involved 16 clinical laboratories and used SeraCare SNP-matched normal and diseased cell lines as contrived TMB reference materials.
- Memorial Sloan Kettering Cancer Center developed a liquid biopsy assay for genomic profiling. The CLIA-approved assay, MSK-ACCESS, is used for the routine clinical assessment of thousands of cancer patient samples. Contrived ctDNA reference materials from LGC Clinical Diagnostics | SeraCare helped validate the assay’s sensitivity and specificity.
- UK National External Quality Assessment Service used SeraCare’s ctDNA reference materials for its standardization analysis and external quality assessments for all labs in the UK that perform EGFR mutation plasma testing. A consortium of five European EQA providers collaborated on a broader assessment of 310 laboratories (in 44 countries) with LGC Clinical Diagnostics | SeraCare contrived reference materials that included custom-manufactured plasma samples.
Stay on top of the evolving field of cancer diagnostics
LGC Clinical Diagnostics | SeraCare provides a comprehensive portfolio of reference materials available in DNA, ctDNA, RNA, or FFPE formats. We can manufacture custom materials to meet your specifications, full traceability, and any required QA level offering unparalleled flexibility and scalability for validating your NGS workflow. We're committed to being a part of the development and validation of emerging NGS methods.
Want to learn more?
Download the white paper titled The critical role of NGS reference materials in precision oncology applications, by clicking here, or on the button below.
