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

BMC Medical Genetics

Technical Advance

Laszlo Füzesi¹  Julia Kitz¹  Florian Haller²  Regine Schneider-Stock³  Ronald Simon⁴  Antje Krohn⁴  Sabine Merkelbach-Bruse⁵  Eva Wardelmann⁵  Hans-Ulrich Schildhaus⁵  Wolfgang Dietmaier⁶  Andreas Gaumann⁶  Gunhild Mechtersheimer⁷  Roland Penzel⁷ 

[1] Department of Gastroenteropathology, Georg-August University Göttingen, Robert-Koch-Str. 40, D-37075, Göttingen, Germany;Department of Gastroenteropathology, Georg-August University Göttingen, Robert-Koch-Str. 40, D-37075, Göttingen, Germany;Department of Pathology, Albert-Ludwig University, D-79098, Freiburg, Germany;Department of Pathology, Otto von Guericke University, Leipziger Str. 44, D-39120, Magdeburg, Germany;Department of Pathology, University of Erlangen, D-91054, Erlangen, Germany;Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246, Hamburg, Germany;Department of Pathology, University of Bonn Medical School, Sigmund-Freud-Str. 25, D-53127, Bonn, Germany;Department of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, D-93053, Regensburg, Germany;Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, D-69120, Heidelberg, Germany;

关键词: Imatinib;    Mutation Analysis;    Gastrointestinal Stromal Tumor;    PDGFRA Mutation;    Human Genome Variation Society;   

DOI  :  10.1186/1471-2350-11-106

 received in 2009-12-31, accepted in 2010-07-04,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMutation 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.MethodsWhen 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.ResultsWe 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.ConclusionsBy 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.

【 授权许可】

CC BY   
© Merkelbach-Bruse et al; licensee BioMed Central Ltd. 2010