Tumor Mutational Burden

Tumor mutational burden (TMB) is the most promising genotyping biomarker for immuno-oncology (I-O) therapeutic response, but its clinical application depends on accurate, consistent measurement by targeted NGS panels. SeraCare is working with industry experts to build custom TMB reference standards to standardize and harmonize TMB measurements across NGS assays. These standards will ensure the precision and accuracy of NGS TMB measurements for patient stratification in I-O checkpoint inhibitor trial projects and proficiency testing programs. We are currently developing and delivering custom TMB reference standards to organizations throughout the world, so contact us for build-to-order standards for your TMB assay validation project today.

Concordance of SeraCare TMB reference standard cell lines to COSMIC WES data

Tissue Disease SeraCare WES* COSMIC WES**
Breast Ductal Carcinoma 4.45 4.24
Lung SCLC 7.13 7.44
Lung NSCLC 20.31 19.66
Lung Adenocarcinoma 26.38 25.13


Global Efforts are Underway

  • IQN Path has chosen SeraCare to supply a range of genomic DNA and FFPE TMB reference standards featuring confirmed low, mid, and high levels of mutational burdens in the exome regions for the first-ever global TMB proficiency testing program. This scheme will involve about 30 labs who are monitoring TMB as part of their cancer tumor profiling assays by NGS.
  • SeraCare is the sole provider of materials to inform the development of TMB reference standards to Friends of Cancer Research’s TMB Harmonization Working Group; a consortium of clinical, regulatory, and industry experts working on harmonizing TMB measurements by targeted NGS panels. Now in phase two, this project aims to develop a consensus solution on how to standardize methods for calculating and reporting TMB measurement and advance patient care.
  • SeraCare KOL TMB Working Group  - comprised of industry experts in NGS assay development, pharma/biopharma, cancer research and treatment hospitals, as well as clinical reference laboratories – meets regularly to inform the development of TMB reference standards for analytical validation of targeted NGS panels for clinical trial projects.

Rely on Our Expertise

SeraCare is a globally recognized leader in NGS tumor profiling reference materials and QC data management solutions. NGS panel manufacturers and clinical testing laboratories rely on our broad portfolio of highly multiplexed RNA and DNA reference standards to accelerate their assay development, validation, and clinical deployment for cancer patient testing.

And with SeraCare’s VariantFlex™ custom NGS library, you can easily get the variants you need at your desired allele frequencies in the format that fits your assay within weeks, thanks to our streamlined process and flexible biosynthetic technology.

Ready to discuss your blood or tissue-based TMB reference standard needs? Contact us today. 

Contact Us to Get Started

*SeraCare WES was generated using an Agilent SureSelectXT2 Human All Exon V6 +COSMIC target enrichment kit and sequenced on an Illumina NovaSeqTM 6000.  Sequence reads were aligned to the hg38 genome assembly with BWA-MEM1 and variants were called with Mutect22.  Variants were filtered using criteria described by the Friends of Cancer Research TMB Harmonization Working Group (personal communication).

**Mutation data was taken from the Catalog of Somatic Mutations in Cancer database and filtered to remove silent mutations and the same mutations annotated in one or more transcripts were condensed to a single representation.

1. Li, H. and Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler Transform. Bioinformatics. 25,1754-60 (2009).

2. Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213–219 (2013).