title: A quality control program for mutation detection in KIT and PDGFRA in gastrointestinal stromal tumours.
abstract: BACKGROUND
  Although most gastrointestinal stromal tumours (GIST) carry oncogenic mutations in KIT exons 9, 11, 13 and 17, or in platelet-derived growth factor receptor alpha (PDGFRA) exons 12, 14 and 18, around 10% of GIST are free of these mutations. Genotyping and accurate detection of KIT/PDGFRA mutations in GIST are becoming increasingly useful for clinicians in the management of the disease.
  
  
  METHODS
  To evaluate and improve laboratory practice in GIST mutation detection, we developed a mutational screening quality control program. Eleven laboratories were enrolled in this program and 50 DNA samples were analysed, each of them by four different laboratories, giving 200 mutational reports.
  
  
  RESULTS
  In total, eight mutations were not detected by at least one laboratory. One false positive result was reported in one sample. Thus, the mean global rate of error with clinical implication based on 200 reports was 4.5%. Concerning specific polymorphisms detection, the rate varied from 0 to 100%, depending on the laboratory. The way mutations were reported was very heterogeneous, and some errors were detected.
  
  
  CONCLUSIONS
  This study demonstrated that such a program was necessary for laboratories to improve the quality of the analysis, because an error rate of 4.5% may have clinical consequences for the patient.
authors.affiliation: Department of Pathology, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux Cedex, France. hostein@bergonie.org
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hostein
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Sylvianne
authors.initials: S
authors.lastname: Olschwang
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Bringuier
authors.forename: Louisa
authors.initials: L
authors.lastname: Toffolati
authors.forename: David
authors.initials: D
authors.lastname: Gonzalez
authors.forename: Sébastien
authors.initials: S
authors.lastname: Forget
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
authors.forename: Lucyna
authors.initials: L
authors.lastname: Morzuch
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Nicolas
authors.initials: N
authors.lastname: Faur
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Paolo
authors.initials: P
authors.lastname: Dei Tos
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007753:Laboratories / Q000592:standards*; D009154:Mutation; D011110:Polymorphism, Genetic; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011786:Quality Control; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha