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Medical Oncology

, Volume 29, Issue 3, pp 1765–1772 | Cite as

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

  • J. F. Emile
  • S. Brahimi
  • J. M. Coindre
  • P. P. Bringuier
  • G. Monges
  • P. Samb
  • L. Doucet
  • I. Hostein
  • B. Landi
  • M. P. Buisine
  • A. Neuville
  • O. Bouché
  • P. Cervera
  • J. L. Pretet
  • J. Tisserand
  • A. Gauthier
  • A. Le Cesne
  • J. C. Sabourin
  • J. Y. Scoazec
  • S. Bonvalot
  • C. L. Corless
  • M. C. Heinrich
  • J. Y. Blay
  • P. Aegerter
Original Paper

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.

Keywords

Epidemiology Sarcoma Gastrointestinal tumor Tyrosine kinase receptor 

Notes

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.

Supplementary material

12032_2011_74_MOESM1_ESM.doc (102 kb)
Supplementary material 1 (DOC 101 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • J. F. Emile
    • 1
    • 2
  • S. Brahimi
    • 1
  • J. M. Coindre
    • 3
  • P. P. Bringuier
    • 4
  • G. Monges
    • 5
  • P. Samb
    • 6
  • L. Doucet
    • 7
  • I. Hostein
    • 3
  • B. Landi
    • 8
  • M. P. Buisine
    • 9
  • A. Neuville
    • 10
    • 18
  • O. Bouché
    • 11
  • P. Cervera
    • 12
  • J. L. Pretet
    • 13
  • J. Tisserand
    • 1
  • A. Gauthier
    • 1
  • A. Le Cesne
    • 14
  • J. C. Sabourin
    • 15
  • J. Y. Scoazec
    • 4
  • S. Bonvalot
    • 14
  • C. L. Corless
    • 16
  • M. C. Heinrich
    • 16
  • J. Y. Blay
    • 17
  • P. Aegerter
    • 6
  1. 1.EA4340, Service de PathologieHôpital Ambroise Paré, Versailles SQY UniversityBoulogneFrance
  2. 2.APHP, Pathology DepartmentAmbroise Paré HospitalBoulogneFrance
  3. 3.Pathology DepartmentBergonié InstituteBordeauxFrance
  4. 4.HCLE Herriot HospitalLyonFrance
  5. 5.Pathology DepartmentPaoli Calmettes InstituteMarseilleFrance
  6. 6.APHP, EA2506, Public Health DepartmentVersailles SQY University, Ambroise Paré HospitalBoulogneFrance
  7. 7.Pathology DepartmentCHU de BrestBrestFrance
  8. 8.APHPGorges Pompidou European HospitalParisFrance
  9. 9.Biochemistry and Molecular Biology DepartmentCHU de LilleLilleFrance
  10. 10.Pathology DepartmentCHU de StrasbourgStrasbourgFrance
  11. 11.CHU de ReimsReimsFrance
  12. 12.APHP, Pathology DepartmentSaint Antoine HospitalParisFrance
  13. 13.Univ Franche-ComteCHU de BesanconBesanconFrance
  14. 14.Gustave Roussy InstituteVillejuifFrance
  15. 15.Pathology DepartmentCHU de RouenRouenFrance
  16. 16.Portland VA Medical CenterOHSU Knight Cancer InstitutePortlandUSA
  17. 17.Léon Bérard CenterLyonFrance
  18. 18.Pathology DepartmentBergonié InstituteBordeauxFrance

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