Progress and potential of RAS mutation detection for diagnostics and companion diagnostics

ABSTRACT

Introduction: The importance of RAS mutation in carcinogenesis is established, and knowledge of an individual cancer’s mutation status is important for optimal treatment.

Areas covered: This paper is restricted to RAS testing in cancer, and highlights papers relevant to current practice.

Expert commentary: Multiple laboratory methods are available for RAS gene analysis. PCR is commonly used to determine RAS status, providing a robust and inexpensive technology for clinical use. Next generation sequencing (NGS) platforms are changing the way in which mutation status is determined, though they require considerable expertise. Pre-analytical issues affect both methods and should be considered. The interpretation and reporting of results is not simple, particularly for NGS. External quality assurance is a pre-requisite for success, and is mandated by most laboratory accreditation schemes. The use of RAS testing is now extending beyond biopsy material to include the detection of mutations in circulating cell-free DNA and tumour cells.

KEYWORDS:

• RAS
• PCR
• sequencing
• colorectal
• lung
• cancer

Acknowledgments

The author is grateful to all those involved in the committees which have contributed to the guidance for molecular pathology: the author would like to take responsibility for any errors in this review.

Declaration of interest

IA. Cree has previously been a member of advisory boards for RAS mutation analysis for Astra-Zeneca, Amgen, Biocartis, Merck, Novartis, Pfizer, and ThermoFisher. He is a member of the Onconetwork consortium developing NGS solutions on the IonTorrent PGM, and a spin-off company, CanTech Ltd, which has funded PCR array development. He is a member of the UKNEQAS Scientific Advisory Board for Molecular Pathology and chairs the Research Committee of the Royal College of Pathologists. All of the views expressed represent the author’s opinion and this is not intended to be a comprehensive or systematic review. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.