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JMD 2004, Vol. 6, No. 3
Copyright © 2004 American Society for Investigative Pathology & Association for Molecular Pathology

Association of Platelet-Derived Growth Factor Receptor Mutations with Gastric Primary Site and Epithelioid or Mixed Cell Morphology in Gastrointestinal Stromal Tumors

Eva Wardelmann^*, Aksana Hrychyk, Sabine Merkelbach-Bruse^*, Katharina Pauls^*, Jennifer Goldstein^*, Peter Hohenberger, Inge Losen^*, Christoph Manegold, Reinhard Büttner^* and Torsten Pietsch

From the Departments of Pathology * and Neuropathology, University of Bonn Medical Center, Bonn, Germany; the Division of Surgery and Surgical Oncology, Robert Roessle Hospital and Tumor Institute at the Max Delbrueck Center for Molecular Medicine, Charite, Campus Berlin-Buch, Humboldt University at Berlin, Berlin, Germany; and Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany

Most gastrointestinal stromal tumors (GISTs) carry activating mutations of the KIT gene encoding the receptor tyrosine kinase KIT. In a previous study we were able to show an association between the lack of KIT mutations (wild-type GISTs) and the presence of a significant epithelioid tumor component. A very recent study described the occurrence of PDGFR mutations in KIT wt GISTS. Therefore, we studied a panel of 87 GISTs for mutations in the hot spot regions of the PDGFR gene with single strand conformation polymorphism analysis and sequencing and correlated the PDGFR status with pathomorphological data. We detected 20 cases with exon 18 mutations but none with exon 12 mutations. The mutations were located in the second kinase domain of PDGFR with 16 point mutations, and four larger deletions of 9 to 12 bp. All cases with mutations in the PDGFR gene revealed wild-type KIT in common regions of mutation, ie, exons 9 and 11. Most interestingly, the occurrence of PDGFR mutations was significantly associated with a higher frequency of epithelioid or mixed morphology (18 of 20 cases, P < 0.0001) and gastric location (all cases, P = 0.0008). Our data indicate that GISTs represent distinctive entities, differing in genetic, biological, and morphological features.

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