title: Mutational spectrum and therapy response of metastasized GIST in Central Switzerland - a population-based study.
abstract: BACKGROUND
  Until now, no population-based studies investigated the mutational status of primary GIST (PT) and corresponding metastases and correlated these data with response to Imatinib or Sunitinib therapy.
  
  
  METHODS
  In a retrospective observation study, all metastatic GISTs of the last 15years of our institution were investigated for mutations in c-kit and in PDGFRα gene in each PT and corresponding metastasis. Correlation with clinical outcome and response to Imatinib or Sunitinib therapy was performed.
  
  
  RESULTS
  In 13 PT c-kit mutations in exon 9 (3), exon 11 (7) and exon 13 (1), 2 wild type genotypes, and no PDGFRα mutation were detected. In three metastases a switch from heterozygosity to homozygosity and one additional exon 13 mutation was observed. All 10 persons with available follow-up received Imatinib as first-line chemotherapy. Five of them (3 exon 9 mutations, 1 wild type, 1 additional exon 13 mutation) stopped Imatinib due to tumour progression. In three cases, Sunitinib as second-line chemotherapy was ended due to the same reasons.
  
  
  CONCLUSIONS
  Our data support previous observations, that PDGFRα mutations play no important role in metastasized GISTs. The influence of Imatinib and Sunitinib therapy in metastasized GISTs with wild type genotype and c-kit exon 9 mutations needs further investigation.
authors.affiliation: Institute of Pathology, Luzerner Kantonsspital, Lucerne, Switzerland. matthias.roessle@usz.ch
authors.forename: Matthias
authors.initials: M
authors.lastname: Rössle
authors.forename: Astrid
authors.initials: A
authors.lastname: Hirschmann
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001549:Benzamides; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D018450:Disease Progression; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D005828:Genetics, Population; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012189:Retrospective Studies; D000077210:Sunitinib; D013557:Switzerland
chemical_list: D001549:Benzamides; D017931:DNA Primers; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib