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  • Next-generation sequencing demonstrates the rarity of short kinase variants specific to quadruple wild-type gastrointestinal stromal tumours

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Next-generation sequencing demonstrates the rarity of short kinase variants specific to quadruple wild-type gastrointestinal stromal tumours
  1. Newton A C S Wong1,2,
  2. Olivier T Giger3,
  3. Rogier ten Hoopen4,
  4. Ruth T Casey5,
  5. Kirsty Russell2,
  6. Claire Faulkner2
  1. 1 Department of Cellular Pathology, Southmead Hospital, Bristol, UK
  2. 2 South West Genomic Laboratory Hub, Southmead Hospital, Bristol, UK
  3. 3 Department of Pathology, University of Cambridge, Cambridge, UK
  4. 4 Department of Oncology, University of Cambridge, Cambridge, UK
  5. 5 Department of Medical Genetics, University of Cambridge, Cambridge, UK
  1. Correspondence to Dr Newton A C S Wong, Department of Cellular Pathology, Southmead Hospital, Bristol BS10 5NB, UK; Nacs.Wong{at}bristol.ac.uk

Abstract

Aim There is no known specific biomarker or genetic signal for quadruple wild-type (qWT) gastrointestinal stromal tumours (GISTs). By next-generation sequencing (NGS) of different GIST subgroups, this study aimed to characterise such a biomarker especially as a potential therapeutic target.

Methods and results An NGS panel of 672 kinase genes was applied to DNA extracted from 11 wild-type GISTs (including three qWT GISTs) and 5 KIT/PDGFRA mutated GISTs. Short variants which were present in qWT GISTs but no other GIST subgroup were shortlisted. After removing common population variants, in silico-classified deleterious variants were found in CSNK2A1, MERTK, RHEB, ROCK1, PIKFYVE and TRRAP. None of these variants were demonstrated in a separate cohort of four qWT GISTs.

Conclusions Short kinase variants which are specific to qWT GISTs are rare and are not universally demonstrated by this whole subgroup. It is therefore possible that the current definition of qWT GIST still covers a heterogenous population.

  • gastrointestinal neoplasms
  • genetics
  • molecular biology

https://doi.org/10.1136/jclinpath-2020-206613

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    Footnotes

    • Handling editor Cheok Soon Lee.

    • Twitter @krussyo

    • Contributors NACSW conceived the idea for the study. NACSW, OTG, RtH and RTC assembled the study cohorts. KR, CF and NACSW performed and/or interpreted the genetic analyses. All authors contributed to the manuscript.

    • Funding This study was funded by a research grant from GIST Cancer UK.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval This study was approved by the UK National Research Ethics Service (REC reference no: 15/NW/0555).

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