Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502_503dup and KIT exon 11 557_559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.
BACKGROUND: KIT exon 11 mutations are observed in 60% of gastrointestinal stromal tumours (GIST). Exon 11 codes for residues Tyr568 and Tyr570, which play a major role in signal transduction and degradation of KIT. Our aim was to compare the outcome of patients with deletion of both Tyr568 -570 (delTyr) and the most frequent deletion delWK557 -558 (delWK). METHODS: Pathology and clinical characteristics of 68 patients with delTyr (n ¼ 26) or delWK (n ¼ 42) were reviewed and compared. RESULTS: GISTs with delTyr were more frequently extragastric than those with delWK (69 vs 26%, Po0.0005). After curative surgery, median relapse-free survival were 10.8 and 11.1 months for patients with delTyr (n ¼ 14) and delWK (n ¼ 29), respectively (P ¼ 0.92). All patients treated with imatinib for a non-resectable or metastatic GIST had an objective response (n ¼ 15) or a stable disease (n ¼ 21) as best response, regardless of mutation. Median progression-free survival with imatinib were 21.9 and 18.9 months for patients with GIST with delTyr (n ¼ 14) and delWK (n ¼ 22), respectively (P ¼ 0.43). CONCLUSION: In this large retrospective series, the type of KIT exon 11 mutation was correlated with the origin of GIST, but not with prognosis or response to imatinib.
Human urine was considered sterile for a long time. However, 416 species have been previously cultured, including only 40 anaerobic species. Here, we used culturomics, particularly those targeting anaerobes, to better understand the urinary microbiota. By testing 435 urine samples, we isolated 450 different bacterial species, including 256 never described in urine of which 18 were new species. Among the bacterial species identified, 161 were anaerobes (35%). This study increased the known urine repertoire by 39%. Among the 672 bacterial species isolated now at least once from urine microbiota, 431 (64.1%) were previously isolated from gut microbiota, while only 213 (31.7%) were previously isolated from vagina. These results suggest that many members of the microbiota in the urinary tract are in fact derived from the gut, and a paradigm shift is thus needed in our understanding.
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