Duplex Sequencing Technology Detects Early Carcinogen-Caused Mutagenesis

A new study validates the application of duplex sequencing in detecting mutations caused by chemical carcinogens.

A recent peer-reviewed study published in Proceedings of the National Academy of Sciences (PNAS) found that TwinStrand Biosciences’ Duplex Sequencing Technology identified and characterized ultra-low frequency gene mutations and early cancer growth caused by carcinogens in mouse models. The study validates the application of the test in detecting the mutagenic activity of chemical carcinogens.1

Precision medicine has seen great strides in recent years, and in cancer care specifically, the use of immunotherapies and targeted therapies has grown as the benefits to patients across cancer types become clearer and more targets are identified. But to identify patients eligible for those therapies and successfully implement them, accurate diagnostic testing is key.

As targeted therapies have gained traction, so has the use of next-generation sequencing (NGS), which identifies gene mutations that make patients eligible for those treatments. The Biochemistry and cloud-based Duplex Sequencing is a software enhancement to existing NGS platforms called error-corrected NGS (ecNGS). It can improve the accuracy of testing 10,000-fold, which allows clinicians and researchers to discover rare DNA mutations that only present faint signals.

The new study, which was conducted by researchers at Millipore Sigma/BioReliance Toxicology Services and Amgen, focused on the assay’s ability to detect mutagenesis, which is the formation of new genetic mutations. Currently, the tools available to do so have limitations, including the need to use bacteria or genetically-modified organisms, which only provide a limited, indirect measurement of mutagenesis.

“The unprecedented richness of data unlocked through Duplex Sequencing will contribute to the revitalization of genetic toxicology and mutational science and will help expedite numerous fields of research and development," Jesse Salk, MD, PhD, CEO of TwinStrand Biosciences, said in a statement.2

Duplex sequencing was shown to be accurate in detecting carcinogen-induced mutations in 5 tissues in 2 strains of mice. The mutations were caused by 3 distinct carcinogens, and they were detected less than a month after exposure. In a cancer-predisposed mouse strain, the test detected early signs of cancer before microscopic tumor formation was visible.

“Error-corrected next-generation sequencing can be used to rapidly detect and quantify the in vivo mutagenic impact of environmental exposures or endogenous processes in any tissue, from any species, at any genomic location,” the authors wrote. “The greater speed, higher scalability, richer data outputs, and cross-species and cross-locus applicability of ecNGS compared to existing methods make it a powerful new tool for mutational research, regulatory safety testing, and emerging clinical applications.”

Catching cancer early has been shown to benefit both patient outcomes and the system, since later stage cancers are typically more complicated to treat and require more extensive therapies. The new study has the potential to expand the real-world application of Duplex Sequencing both in preclinical drug research and for in-human use to non-invasively identify exposure to carcinogens in the environment, which could aid public health officials with surveillance and source control, Salk said.


1. Valentine CC, Young RR, Fielden MR, et al. Direct quantification of in vivo mutagenesis and carcinogenesis using duplex sequencing. Proc Natl Acad Sci. Published online December 14, 2020. doi:10.1073/pnas.2013724117/

2. TwinStrand Biosciences Announces Peer-Reviewed Publication of Study Results Highlighting Ability of Duplex Sequencing Technology to Rapidly Detect the Mutagenic Activity of Chemicals. News release. TwinStrand Biosciences, Inc; December 15, 2020. Accessed December 18, 2020. https://www.prnewswire.com/news-releases/twinstrand-biosciences-announces-peer-reviewed-publication-of-study-results-highlighting-ability-of-duplex-sequencing-technology-to-rapidly-detect-the-mutagenic-activity-of-chemicals-301192486.html

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