August 2018

The NML publishes first digital PCR reference method for quantifying a clinically relevant genetic change

An international group of scientists led by the National Measurement Laboratory (NML), hosted here at LGC, have recently published a paper in Clinical Chemistry demonstrating the applicability of digital PCR (dPCR) as a reference measurement procedure for the quantification of DNA changes relevant to cancer treatment. This method is unique in molecular genetic measurement as it is traceable to the International System of Units (SI) on the basis of counting individual DNA molecules.

Identification and targeting of specific genetic sequences forms the basis of many promising advanced healthcare solutions such as: precision (personalised) medicine in cancer, gene therapies to end genetic disorders in children and the detection of pathogenic and non-pathogenic bacteria in a wide spectrum of infectious and autoimmune diseases. However, the new methods and technologies currently being developed will only achieve their full potential if we can ensure they are safe and can be implemented reproducibly. High accuracy reference methods are one of the key factors in supporting their development into routine application.

Using tests for guiding treatment of colorectal cancer as a model, this paper assessed how a range of dPCR assays and platforms compared and how precisely they measured the cancer mutation. Reproducibility of the selected method was demonstrated through an inter-laboratory study of clinical and National Measurement Institute laboratories. The reference method was additionally validated using an independent approach (ICP-MS) based on chemical analysis. Together these results demonstrate the unprecedented accuracy of dPCR for copy number concentration of a frequently occurring gene mutation used to determine drug treatment.

This study has demonstrated high-accuracy measurements using dPCR can be used to support the traceable standardisation, translation and implementation of molecular diagnostic procedures that will enable advancements in precision medicine. The availability of a primary reference measurement procedure will underpin accreditation requirements for molecular diagnostics, furthering regulatory development and compliance, and ultimately improving patient safety and care.

The work performed at the NML here at LGC provides a foundation for ongoing global discussions around the measurement framework required to support wider biological measurements.
Whale et al. Assessment of Digital PCR as a Primary Reference Measurement Procedure to Support Advances in Precision Medicine. Clin Chem (2018) DOI: 10.1373/clinchem.2017.285478
For further information on our work, and to discover more about our new dPCR Measurement Facility, please contact us.