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A quality control program for mutation detection in KIT and PDGFRA in gastrointestinal stromal tumours

  • Original Article—Alimentary Tract
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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.

Method

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.

Conclusion

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.

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Acknowledgments

This work was supported by CONTICANET (Connective Tissue Cancers Network to Integrate European Experience in Adults and Children), Lyon, France. We are grateful to Pippa McKelvie-Sebileau for help with the English manuscript.

Author information

Authors and Affiliations

  1. Department of Pathology, Institut Bergonié, 229 cours de l’Argonne, 33076, Bordeaux cedex, France

    Isabelle Hostein, Nicolas Faur & Jean-Michel Coindre

  2. Department of Human Genetics, University of Leuven, Leuven, Belgium

    Maria Debiec-Rychter

  3. Centre de Recherche en Cancérologie de Marseille INSERM U891, Institut Paoli-Calmettes, Marseille, France

    Sylvianne Olschwang

  4. Laboratory of Pathology, Edouard Herriot Hospital, Lyon, France

    Pierre-Paul Bringuier

  5. Department of Pathology, CA Foncello Hospital, Treviso, Italy

    Louisa Toffolati & Paolo Dei Tos

  6. Department of Hemato-Oncology, The Institute of Cancer Research, Sutton, UK

    David Gonzalez

  7. Department of Biology and Pathology, Institute of Cancerology Gustave Roussy, Paris, France

    Sébastien Forget

  8. Biology and Pathological Laboratory, Lille Hospital, Lille, France

    Fabienne Escande

  9. Department of Biology and Genetics, Medical University of Gdansk, Gdańsk, Poland

    Lucyna Morzuch

  10. Laboratory of Experimental Pathology, Foundation IRCCS Tumor Institute, Milan, Italy

    Elena Tamborini & Silvana Pilotti

  11. Department of Pathology, Ambroise Pare Hospital, Boulogne, France

    Jean-François Emile

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  1. Isabelle Hostein
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  14. Jean-François Emile
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Correspondence to Isabelle Hostein.

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Hostein, I., Debiec-Rychter, M., Olschwang, S. et al. A quality control program for mutation detection in KIT and PDGFRA in gastrointestinal stromal tumours. J Gastroenterol 46, 586–594 (2011). https://doi.org/10.1007/s00535-011-0375-0

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  • DOI: https://doi.org/10.1007/s00535-011-0375-0

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