Gene-expression profiling to classify soft-tissue sarcomas.
نویسندگان
چکیده
channels triggers the preconditioned state by generating free radicals.sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection. et al. Loss of preconditioning by attenuated activation of myocardial ATP-sensitive potassium channels in elderly patients undergoing coronary angioplasty. enhances myocardial protection in patients undergoing open heart surgery. Prodromal unstable angina in acute myocardial infarction: prognostic value of short-and long-term outcome and predictor of infarct size. cardioprotection in patients with acute myocardial infarction treated with primary percutaneous transluminal coronary angioplasty: assessment with thallium-201/iodine-123 BMIPP dual SPECT. Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction. Increased left ventricular dysfunction in elderly patients despite successful thrombolysis: the GUSTO-1 angiographic experience. effect of prodromal angina pectoris is lost in elderly patients with acute myocardial infarction. differences in biological behaviour, predict responsiveness to treatment, and may identify new molecular targets (panel). Routine immunohistochemistry can be considered as a single-gene expression study; expression profiling gives a holistic view, while lacking topographical information. Nielsen and colleagues analysed 41 soft-tissue tumours, which gave over 1·5 million data points. These profiles were obtained with two different microarrays. Bias from the two arrays was successfully removed by a method known as singular value decomposition. This mathematical technique allows the recognition of the dominant gene (eigengene) and the corresponding array expression (eigenarray), which will facilitate the comparison of data from different arrays. Against the gene-expression profile of 5520 well-measured genes, displaying predefined variation across the different specimens, the 41 sarcomas could be separated into five distinct groups: gastrointestinal stromal tumours, synovial sarcomas, the benign peripheral-nerve-sheath tumours, half the leiomyosarcomas, and a broad group containing all the malignant fibrous histiocytomas, the liposarcomas, and the other leiomyosarcomas. This separation of half of the sarcomas, classified morphologically as leiomyosarcomas, into a cluster characterised by 24 highly expressed genes, gives at least three groups previously grouped together: the gastrointestinal stromal tumours, and the calponin-positive and the calponin-negative leiomyosarcomas. Most gastrointestinal stromal tumours have a gain-of-function mutation in the proto-oncogene KIT, which activates tyrosine kinase. This observation led to the molecular therapy, imatinib mesylate, a KIT-kinase inhibitor. 2 In the Nielsen study a cluster of 125 genes were highly expressed, which separated the gastrointestinal stromal tumours from the other sarcomas. These results and others 3 strengthen the case for separating gastroin-testinal stromal tumours from other leiomyosarcomas, and support the hypothesis of phenotypic …
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ورودعنوان ژورنال:
- Lancet
دوره 359 9314 شماره
صفحات -
تاریخ انتشار 2002