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

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.