Complex genotype in a GIST patient.
Genotipo complejo en un paciente con GIST.
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The case of a 35-year-old man is presented; he was diagnosed as having a gastrointestinal stromal tumour (GIST) which was located in the proximal jejunum and stratified as being high risk. The primary GIST was resected without evidence of relapse until multiple hepatic lesions were documented so that treatment with 400 mg/day imatinib (Glivec®) was begun. After progression was found, the inhibitor dose was increased without response, meaning that 50 mg/day sunitinib (Sutent®) was begun with the same result. The histotype and genotyping were thus re-evaluated, positivity for KIT gene exon 9 mutation being found; 400 mg BID sorafenib (Nexavar®) was administered from November 2009 onwards, achieving a 50% metabolic response (evaluated by PET/CAT) and partial response following the criteria described by Choi and coworkers. A new biopsy of the tumour was made during third-line treatment, demonstrating a complex genotype including the BRAF V600E mutation. Clinical benefit was maintained with the aforementioned intervention until July 2011; the patient was still alive at this point. A detailed analysis of the molecular mechanisms explaining resistance to tyrosine kinase inhibitors and the implications concerning GIST therapy was then proposed.
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