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How close are we to standardised extended RAS gene mutation testing? The UK NEQAS evaluation
  1. Susan D Richman1,
  2. Jennifer Fairley2,
  3. Rachel Butler3,
  4. Zandra C Deans2
  1. 1Department of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St James University Hospital, Leeds, UK
  2. 2UK NEQAS for Molecular Genetics, Department of Laboratory Medicine, The Royal Infirmary, Edinburgh, UK
  3. 3Cardiff and Vale UHB-Medical Genetics University Hospital of Wales, Cardiff, Wales, UK
  1. Correspondence to Dr Zandra C Deans, UK NEQAS for Molecular Genetics, Department of Laboratory Medicine, The Royal Infirmary, Edinburgh EH16 4SA, UK; Sandi.Deans{at}


Aims Since 2008, KRAS mutation status in exon 2 has been used to predict response to anti-EGFR therapies. Recent evidence has demonstrated that NRAS status is also predictive of response. Several retrospective ‘extended RAS’ analyses have been performed on clinical trial material. Despite this, are we really moving towards such extended screening practice in reality?

Methods Data were analysed from four consecutive UK National External Quality Assessment Service for Molecular Genetics Colorectal cancer External Quality Assessment schemes (during the period 2014–2016), with up to 110 laboratories (worldwide) participating in each scheme. Testing of four or five tumour samples is required per scheme. Laboratories provided information on which codons were routinely screened, and provided genotyping and interpretation results for each sample.

Results At least 85% of laboratories routinely tested KRAS codons 12, 13 and 61. Over the four schemes, an increasing number of laboratories routinely tested KRAS codons 59, 117 and 146. Furthermore, more laboratories were introducing next generation sequencing technologies. The pattern of ‘extended testing’ was reassuringly similar for NRAS, although fewer laboratories currently test for mutations in this gene. Alarmingly, still only 36.1% and 24.1% of participating laboratories met the ACP Molecular Pathology and Diagnostics Group and American Society of Clinical Oncology guidelines, respectively, for extended RAS testing in the latest assessment.

Conclusions Despite recommendations in the UK and USA on extended RAS testing, there has clearly been, based on these results, a delay in implementation. Inadequate testing results in patients being subjected to harmful treatment regimens, which would not be the case, were routine practice altered, in line with evidence-based guidelines.

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  • Handling editor Runjan Chetty

  • Contributors All authors were involved in the analysis and interpretation of data, writing the manuscript and in the decision to submit for publication. The corresponding author had full access to the study data and final responsibility for the decision to submit for publication.

  • Funding SDR was funded by Medical Research Council (MRC)-SCORT. ZCD and JF were funded by UK NEQAS for Molecular Genetics.

  • Disclaimer SDR and RB have received honoraria from UK NEQAS for Molecular Genetics.

  • Competing interests SDR, honoraria from UK NEQAS for Molecular Genetics; RB, honoraria from Astra Zeneca, Merck, Pfizer and UK NEQAS for Molecular Genetics; advisory role payments from Astra Zeneca and Merck; additional expenses from Astra Zeneca, Merck and Pfizer; ZCD, honoraria from Astra Zeneca; advisory role payments from Astra Zeneca, Amgen and Pfizer.

  • Provenance and peer review Not commissioned; externally peer reviewed.