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Pitfalls in mutational testing and reporting of common KIT and PDGFRA mutations in gastrointestinal stromal tumors

Sabine Merkelbach-Bruse1*, Wolfgang Dietmaier2, Laszlo Füzesi3, Andreas Gaumann2, Florian Haller38, Julia Kitz3, Antje Krohn4, Gunhild Mechtersheimer5, Roland Penzel5, Hans-Ulrich Schildhaus1, Regine Schneider-Stock67, Ronald Simon4 and Eva Wardelmann1

Author Affiliations

1 Department of Pathology, University of Bonn Medical School, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany

2 Department of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, D-93053 Regensburg, Germany

3 Department of Gastroenteropathology, Georg-August University Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany

4 Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany

5 Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, D-69120 Heidelberg, Germany

6 Department of Pathology, Otto von Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany

7 Department of Pathology, University of Erlangen, D-91054 Erlangen, Germany

8 Department of Pathology, Albert-Ludwig University, D-79098 Freiburg, Germany

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BMC Medical Genetics 2010, 11:106  doi:10.1186/1471-2350-11-106

Published: 4 July 2010



Mutation analysis of KIT and PDGFRA genes in gastrointestinal stromal tumors is gaining increasing importance for prognosis of GISTs and for prediction of treatment response. Several groups have identified specific mutational subtypes in KIT exon 11 associated with an increased risk of metastatic disease whereas GISTs with PDGFRA mutations often behave less aggressive. Furthermore, in advanced GIST disease with proven KIT exon 9 mutation the doubled daily dose of 800 mg imatinib increases the progression free survival and is now recommended both in the European and the American Guidelines. In Germany, there are still no general rules how to perform mutational analysis.


When comparing results from six different molecular laboratories we recognized the need of standardisation. Six German university laboratories with experience in mutation analysis in GISTs joined together to develop recommendations for the mutation analysis of the most common and clinically relevant hot spots, i. e. KIT exons 9 and 11 and PDGFRA exon 18. We performed a three-phased interlaboratory trial to identify pitfalls in performing molecular analysis in GISTs.


We developed a design for a continuous external laboratory trial. In 2009 this external trial was conducted by 19 laboratories via the initiative for quality assurance in pathology (QuiP) of the German Society of Pathology and the Professional Association of German Pathologists.


By performing a three-phased internal interlaboratory trial and conducting an external trial in Germany we were able to identify potential pitfalls when performing KIT and PDGFRA mutational analysis in gastrointestinal stromal tumors. We developed standard operation procedures which are provided with the manuscript to allow other laboratories to prevent these pitfalls.