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Results of the UK NEQAS for Molecular Genetics reference sample analysis
  1. Susan D Richman1,
  2. Jennifer Fairley2,
  3. Jacqueline A Hall2,
  4. Nakul Nataraj3,
  5. Mrudul Bhide3,
  6. Aron Lau3,
  7. Kara L Norman3,
  8. Zandra C Deans2
  1. 1 Department of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St James University Hospital, Leeds, UK
  2. 2 UK NEQAS for Molecular Genetics, Department of Laboratory Medicine, The Royal Infirmary, Edinburgh, UK
  3. 3 Thermo Fisher Scientific, Fremont, California, USA
  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 In addition to providing external quality assessment (EQA) schemes, United Kingdom National External Quality Assessment service (UK NEQAS) for Molecular Genetics also supports the education of laboratories. As an enhancement to the Molecular Pathology EQA scheme, a human cell-line reference sample, manufactured by Thermo Fisher Scientific (AcroMetrix), was provided for analysis. This contained many variants, present at frequencies between 1% and 17.9%.

Methods One hundred and one laboratories submitted results, with a total of 2889 test results on 53 genes being reported. Known polymorphisms, 46/2889 (1.59%) results, were excluded. Variants detected in the seven most commonly reported (and clinically relevant) genes, KRAS, NRAS, BRAF, EGFR, PIK3CA, KIT and PDGFRA, are reported here, as these genes fall within the scope of UK NEQAS EQA schemes.

Results Next generation sequencing (NGS) was the most commonly performed testing platform. There were between 5 and 27 validated variants in the seven genes reported here. Eight laboratories correctly reported all five NRAS variants, and two correctly reported all eight BRAF variants. The validated mean variant frequency was lower than that determined by participating laboratories, with single-gene testing methodologies showing less variation in estimated frequencies than NGS platforms. Laboratories were more likely to correctly identify clinically relevant variants.

Conclusions Over 100 laboratories took the opportunity to test the ‘educational reference sample’, showing a willingness to further validate their testing platforms. While it was encouraging to see that the most widely reported variants were those which should be included in routine testing panels, reporting of variants was potentially open to interpretation, thus clarity is still required on whether laboratories selectively reported variants, by either clinical relevance or variant frequency.

  • EQA
  • colorectal cancer
  • lung cancer
  • melanoma

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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  • Handling editor Runjan Chetty.

  • Contributors All authors made substantial contributions to the manuscript concept, critical revision for intellectual content, final approval of the submitted version and are accountable for all aspects of the work.

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

  • Competing interests NN, MB, AL and KLN were employed by Thermo Fisher Scientific. Other authors have no competing interest to declare.

  • Patient consent Not required.

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

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