The UK NEQAS for Molecular Genetics scheme for gastrointestinal stromal tumour: findings and recommendations following four rounds of circulation

J Clin Pathol. 2012 Sep;65(9):786-90. doi: 10.1136/jclinpath-2012-200851. Epub 2012 Jun 9.


Aims: To describe the UK NEQAS for Molecular Genetics scheme for gastrointestinal stromal tumour (GIST) and to report and interpret the findings of four rounds of circulation of this quality assurance programme for KIT/PDGFRA mutation analyses.

Methods: Samples of GISTs from formalin-fixed paraffin-embedded tissue blocks were circulated to registered participants of the UK NEQAS for Molecular Genetics scheme for GIST. Three samples were provided per annual circulation from 2008 to 2011 inclusive. The participants were required to analyse the samples for KIT and/or PDGFRA mutations using their routine protocols, and the anonymised participants' reports were assessed and an annual scheme report issued.

Results: The genotyping error rates for the 2008, 2009, 2010 and 2011 circulations were 13%, 33%, 19% and 4%, respectively. These errors were either missed or incorrectly described mutations. There was an overall false negative rate of 2% and false positive rate of 0%. The main recommendations that arose from these circulations were: (1) inclusion of reference accession numbers in reports; (2) avoidance of the term 'heterozygous' when analysing DNA from tumour tissue unless there was certainty that only neoplastic DNA was studied; and (3) the need to screen KIT exons 9, 11, 13 and 17 and PDGFRA exons 12, 14 and 18 before classifying a GIST as 'wild type'.

Conclusions: The UK NEQAS for Molecular Genetics scheme emphasises the potential complexities of KIT/PDGFRA mutation analyses for GISTs and provides recommendations to help optimise such genotyping and reporting. The scheme has also demonstrated its educational value among participating laboratories.

MeSH terms

  • DNA Mutational Analysis / standards*
  • Diagnostic Errors
  • Exons
  • False Negative Reactions
  • False Positive Reactions
  • Gastrointestinal Stromal Tumors / genetics*
  • Genotype
  • Humans
  • Mutation*
  • Observer Variation
  • Practice Guidelines as Topic
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins c-kit / genetics*
  • Quality Assurance, Health Care / standards*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Reproducibility of Results
  • United Kingdom


  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha