title: [Gastrointestinal stromal tumors carrying PDGFRalpha mutations occur preferentially in the stomach and exhibit an epithelioid or mixed phenotype].
abstract: OBJECTIVE
  Most gastrointestinal stromal tumors (GISTs) carry gain-of-function mutations of the KIT gene encoding the receptor tyrosine kinase KIT. However, in a subset of GISTs no activating mutations are detectable in KIT. Recently, PDGFRalpha mutations have been identified as alternative oncogenic mechanism. We studied a panel of 100 GISTs for mutations in hot spot regions of KIT (exons 9, 11, 13 and 17) and PDGFRalpha (exons 12 and 18) and compared the results with pathomorphological and immunohistochemical data.
  
  
  METHODS
  DNA from formalin-fixed and paraffin-embedded tumor tissue was extracted after microdissection from serial sections. We performed single strand conformational polymorphism analysis and direct sequencing.
  
  
  RESULTS
  We found PDGFRalpha mutations in 24 of 55 GISTs with wild-type sequence in exons 9, 11, 13 and 17 of KIT. All mutations were located in exon 18 of the PDGFRca gene which encodes the tyrosine kinase domain II. None of the 45 GISTs with detectable KIT mutation carried a mutation in the PDGFRalpha gene. Interestingly, all PDGFRalpha-mutated tumors were located in the stomach whereas GISTs with exon 9 and 13 KIT mutations occurred predominantly in the small bowel. Additionally, 21 of 24 GISTs carrying PDGFRalpha mutations displayed an epithelioid or mixed phenotype. In contrast, KIT-mutated GISTs exhibited almost always a spindled histology (38 of 45 cases).
  
  
  CONCLUSIONS
  Our analysis provides evidence that GISTS represent distinctive entities with different genetic, biological and phenotypic features.
authors.affiliation: Institut für Pathologie, Universitäitsklinikum Bonn.
authors.forename: E
authors.initials: E
authors.lastname: Wardelmann
authors.forename: K
authors.initials: K
authors.lastname: Pauls
authors.forename: S
authors.initials: S
authors.lastname: Merkelbach-Bruse
authors.forename: A
authors.initials: A
authors.lastname: Hrychyk
authors.forename: I
authors.initials: I
authors.lastname: Losen
authors.forename: P
authors.initials: P
authors.lastname: Hohenberger
authors.forename: R
authors.initials: R
authors.lastname: Büttner
authors.forename: T
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D003937:Diagnosis, Differential; D046152:Gastrointestinal Stromal Tumors / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D013274:Stomach Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha