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Analysis of a large cohort of non-small cell lung cancers submitted for somatic variant analysis demonstrates that targeted next-generation sequencing is fit for purpose as a molecular diagnostic assay in routine practice
  1. David Allan Moore1,2,
  2. Kevin Balbi1,
  3. Alexander Ingham1,
  4. Hendrik-Tobias Arkenau3,
  5. Philip Bennett1
  1. 1 Sarah Cannon Molecular Diagnostics, London, UK
  2. 2 Department of Pathology, UCL Cancer Institute, London, UK
  3. 3 Sarah Cannon Research Institute UK, London, UK
  1. Correspondence to Dr David Allan Moore, Sarah Cannon Molecular Diagnostics, London WC1E 6JSA, UK; d.moore{at}ucl.ac.uk

Abstract

Aims Targeted next-generation sequencing (tNGS) is increasingly being adopted as an alternative to single gene testing in some centres. Our aim was to assess the overall fitness and utility of tNGS as a routine clinical test in non-small cell lung cancer (NSCLC).

Methods All NSCLC cases submitted to a single laboratory for tNGS analysis over a 3-year period were included. Rejection/failure rates and turnaround times were calculated. For reportable cases, data relating to observed genetic changes likely to be driving tumour growth and/or contributing to therapeutic resistance were extracted. The impact of varied referral site practices (tissue processing and sample format submitted) on analytical outcomes was also considered.

Results A total of 2796 cases were submitted, of which 217 (7.8%) were rejected and 131 (5.1%) failed. The median turnaround time was seven working days. Of 2448 reported cases, KRAS, EGFR or other recognised driver mutations were observed in 35%, 17% and 5.4%, respectively. Of the remaining cases, 3.5% demonstrated significant incidental evidence of gene amplification. In 15% of EGFR-driven cases, evidence of an EGFR tyrosine kinase inhibitor resistance mechanism was observed. Potential concerns around the provision of slides or precut ‘rolls’ only (cf, formalin fixed paraffin embedded (FFPE) tissue blocks) as standard practice by certain referral sites were identified.

Conclusions A tNGS panel approach is practically achievable, with acceptable success rates and turnaround times, in the context of a routine clinical service. Furthermore, it provides additional clinically and analytically relevant information, which is not available from single gene testing alone.

  • diagnostics
  • cancer genetics
  • lung cancer
  • molecular pathology

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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors DAM performed data collection and analysis. KB and AI assisted with data collection. DAM and PB wrote the manuscript. PB conceived the project and had oversight throughout. H-TA reviewed the data and the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests PB has participated in ThermoFisher’s European Clinical Oncology Advisory Board meetings, and has delivered sponsored, but not for profit, presentations at the invitation of ThermoFisher UK on a number of occasions. Other authors have no competing interests to declare.

  • Patient consent Not required.

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

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