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Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs

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Abstract

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502_503dup and KIT exon 11 557_559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.

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Acknowledgments

MolecGIST study was supported by grants from Ligue contre le Cancer, Institut National du Cancer (INCa) and unrestricted grants from Novartis Pharma. The authors would like to thank patients who participated to MolecGIST study and their families, as well as all the pathologists, oncologists, surgeons, gastroenterologists, physicians and clinical research assistants who participated to the collection of the data. The list is available on http://www.gist-france.org/remerciements.html.

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Author notes

  1. A. Neuville

    Present address: Pathology Department, Bergonié Institute, Bordeaux, France

Authors and Affiliations

  1. EA4340, Service de Pathologie, Hôpital Ambroise Paré, Versailles SQY University, 92104, Boulogne, France

    J. F. Emile, S. Brahimi, J. Tisserand & A. Gauthier

  2. APHP, Pathology Department, Ambroise Paré Hospital, Boulogne, France

    J. F. Emile

  3. Pathology Department, Bergonié Institute, Bordeaux, France

    J. M. Coindre & I. Hostein

  4. HCL, E Herriot Hospital, Lyon, France

    P. P. Bringuier & J. Y. Scoazec

  5. Pathology Department, Paoli Calmettes Institute, Marseille, France

    G. Monges

  6. APHP, EA2506, Public Health Department, Versailles SQY University, Ambroise Paré Hospital, Boulogne, France

    P. Samb & P. Aegerter

  7. Pathology Department, CHU de Brest, Brest, France

    L. Doucet

  8. APHP, Gorges Pompidou European Hospital, Paris, France

    B. Landi

  9. Biochemistry and Molecular Biology Department, CHU de Lille, Lille, France

    M. P. Buisine

  10. Pathology Department, CHU de Strasbourg, Strasbourg, France

    A. Neuville

  11. CHU de Reims, Reims, France

    O. Bouché

  12. APHP, Pathology Department, Saint Antoine Hospital, Paris, France

    P. Cervera

  13. Univ Franche-Comte, CHU de Besancon, Besancon, France

    J. L. Pretet

  14. Gustave Roussy Institute, Villejuif, France

    A. Le Cesne & S. Bonvalot

  15. Pathology Department, CHU de Rouen, Rouen, France

    J. C. Sabourin

  16. Portland VA Medical Center, OHSU Knight Cancer Institute, Portland, OR, USA

    C. L. Corless & M. C. Heinrich

  17. Léon Bérard Center, Lyon, France

    J. Y. Blay

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  1. J. F. Emile
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  2. S. Brahimi
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  3. J. M. Coindre
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Correspondence to J. F. Emile.

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Emile, J.F., Brahimi, S., Coindre, J.M. et al. Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs. Med Oncol 29, 1765–1772 (2012). https://doi.org/10.1007/s12032-011-0074-y

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  • DOI: https://doi.org/10.1007/s12032-011-0074-y

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