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Influence of cytochrome P450, ABC and SLC gene polymorphisms on imatinib therapy outcome of patients with gastrointestinal stromal tumours (GIST)

K. Wasielewski, B. Wasag, A. Wozniak, J. Pikiel, A. Kowalik, C. Osuch, E. Bylina, J. A. Siedlecki, P. Rutkowski, J. Limon

. 2017 ; 63 (2) : 78-83.

Jazyk angličtina Země Česko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc18020889

The efficacy of imatinib-based therapy depends on the proteins involved in its metabolism and transportation. Therefore, the aim of our study was to investigate the possible correlation of selected P450, ABC and SLC polymorphic variants and the outcome of imatinib therapy. A total of 101 patients with advanced, KIT/PDGFRA(+) GIST treated with imatinib were enrolled to the study. DNA was extracted from peripheral blood samples and genotypes were determined by PCR-RFLP and direct sequencing. Deviation from the Hardy-Weinberg equilibrium was only observed for rs2740574. None of the studied SNPs was associated with GIST time to progression. No significant correlation between any specific variant and time to progression was found in the group with KIT exon 11 mutation. However, individuals of at least three potentially unfavourable genotypes presented significantly shorter time to progression in comparison to patients with two or less unfavourable genotypes.

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$a The efficacy of imatinib-based therapy depends on the proteins involved in its metabolism and transportation. Therefore, the aim of our study was to investigate the possible correlation of selected P450, ABC and SLC polymorphic variants and the outcome of imatinib therapy. A total of 101 patients with advanced, KIT/PDGFRA(+) GIST treated with imatinib were enrolled to the study. DNA was extracted from peripheral blood samples and genotypes were determined by PCR-RFLP and direct sequencing. Deviation from the Hardy-Weinberg equilibrium was only observed for rs2740574. None of the studied SNPs was associated with GIST time to progression. No significant correlation between any specific variant and time to progression was found in the group with KIT exon 11 mutation. However, individuals of at least three potentially unfavourable genotypes presented significantly shorter time to progression in comparison to patients with two or less unfavourable genotypes.
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$a Wasag, B. $u Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland; Laboratory of Clinical Genetics, University Clinical Centre, Gdansk, Poland
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$a Wozniak, A. $u Laboratory of Experimental Oncology, Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals in Leuven, Leuven, Belgium
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$a Pikiel, J. $u Regional Oncology Centre, Gdansk, Poland
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$a Kowalik, A. $u Department of Molecular Diagnostics, Holycross Cancer Centre, Kielce, Poland
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$a Osuch, C. $u Department of General Surgery, Medical Faculty, Jagiellonian University, Krakow, Poland
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$a Bylina, E. $u Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.
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$a Siedlecki, J. A. $u Department of Translational and Molecular Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
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$a Rutkowski, P. $u Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
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$a Limon, J. $u Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland; Laboratory of Clinical Genetics, University Clinical Centre, Gdansk, Poland
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