Mutational spectrum and therapy response of metastasized GIST in Central Switzerland - a population-based study

Eur J Cancer. 2011 Jun;47(9):1305-11. doi: 10.1016/j.ejca.2011.01.012. Epub 2011 Feb 18.

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.

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Benzamides
  • DNA Mutational Analysis*
  • DNA Primers / genetics
  • Disease Progression
  • Exons
  • Female
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology*
  • Gastrointestinal Stromal Tumors / therapy
  • Genetics, Population
  • Humans
  • Imatinib Mesylate
  • Indoles / therapeutic use
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Metastasis
  • Piperazines / therapeutic use
  • Proto-Oncogene Proteins c-kit / genetics
  • Pyrimidines / therapeutic use
  • Pyrroles / therapeutic use
  • Retrospective Studies
  • Sunitinib
  • Switzerland

Substances

  • Benzamides
  • DNA Primers
  • Indoles
  • Piperazines
  • Pyrimidines
  • Pyrroles
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Sunitinib