SeraCare Life Sciences, Milford, Mass, has released the first genomic DNA (gDNA) and formalin-fixed, paraffin-embedded (FFPE) reference materials for the measurement of tumor mutational burden (TMB) via next-generation sequencing (NGS) assays.

TMB is a promising pancancer biomarker for assessing immunooncology drug response. However, measuring TMB is challenging because different targeted NGS panels interrogate different regions and percentages of the genome, and they use different criteria to score relevant somatic mutations. Currently, there is poor correlation among targeted NGS assays that measure TMB at mutation levels that may be relevant for accurately selecting and stratifying cancer patients for immunooncology therapies.

SeraCare collaborated with experts within the Friends of Cancer Research and the International Quality Network for Pathology to develop and evaluate a range of gDNA- and FFPE-based TMB reference materials across different targeted NGS panels, sequencing platforms, and bioinformatics analysis pipelines.

SeraCare was selected to provide FFPE TMB reference materials as part of a pilot program of the International Quality Network for Pathology, and to become one of 16 participating laboratories in the Phase II project of the TMB harmonization working group of the Friends of Cancer Research. Data generated using the reference materials demonstrated their utility for harmonizing and standardizing measurements of TMB by different NGS assays.

Russell Garlick, PhD, SeraCare Life Sciences.

Russell Garlick, PhD, SeraCare Life Sciences.

“Advancing the analytical validation of novel biomarkers through the design and development of fit-for-purpose reference materials is sometimes overlooked as a critical need in our field, but this has not been the case for TMB,” says Russell Garlick, PhD, chief scientific officer for SeraCare. “We partnered with an outstanding panel of scientific experts within our TMB collaborative working group, and this partnership led to the development and rigorous assessment of the first commercial TMB reference materials to harmonize TMB measurements as well as establish clinically actionable results that will enable better patient stratification and treatment outcomes from lifesaving immunooncology therapy.”

Feras Hantash, PhD, Sema4 Genomics.

Feras Hantash, PhD, Sema4 Genomics.

“TMB reference standards are very helpful in establishing accurate TMB measurements on targeted NGS panels and harmonizing with whole-exome sequencing measurements,” says Feras Hantash, PhD, vice president of molecular oncology at Sema4 Genomics, Stamford, Conn. “These materials will assist clinical testing labs in optimizing their NGS panel and bioinformatics pipeline to better support clinical immunooncology trial projects.”

Ravindar Kolhe, MD, Medical College of Georgia at Augusta University.

Ravindra Kolhe, MD, PhD, Medical College of Georgia at Augusta University.

The Seraseq TMB reference materials have been used in the analytical validation of a targeted NGS panel at the Medical College of Georgia. “These TMB reference standards are important in optimizing and standardizing TMB measurements by NGS panels,” says Ravindra Kolhe, MD, PhD, vice chairman of pathology and chief of the section of molecular and genetic pathology at the Medical College of Georgia at Augusta University. “The ability to compare our results not only to whole-exome sequencing but also to other large panels is important for assay validation and QC in a CLIA lab setting.”

For more information, visit SeraCare.