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      Frequent somatic CDH1 loss-of-function mutations in plasmacytoid-variant bladder cancer

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          Abstract

          Plasmacytoid bladder cancer is an aggressive histologic variant with a high risk of disease-specific mortality. Using whole exome and targeted sequencing, we find that truncating somatic alterations in the CDH1 gene occur in 84% of plasmacytoid carcinomas and are specific to this histologic variant. Consistent with the aggressive clinical behavior of plasmacytoid carcinomas, which frequently recur locally, CRISPR/Cas9-mediated knockout of CDH1 in bladder cancer cells enhanced cell migration.

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          Most cited references 6

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          Is Open Access

          BISMA - Fast and accurate bisulfite sequencing data analysis of individual clones from unique and repetitive sequences

          Background Bisulfite sequencing is a popular method to analyze DNA methylation patterns at high resolution. A region of interest is targeted by PCR and about 20-50 subcloned DNA molecules are usually analyzed, to determine the methylation status at single CpG sites and molecule resolution. Results The BISMA (Bisulfite Sequencing DNA Methylation Analysis) software for analysis of primary bisulfite sequencing data implements sequencing data extraction and enhanced data processing, quality controls, analysis and presentation of the methylation state. It uses an improved strategy for detection of clonal molecules and accurate CpG site detection and it supports for the first time analysis of repetitive sequences. Conclusions BISMA works highly automated but still provides the user full control over all steps of the analysis. The BISMA software is freely available as an online tool for academic purposes for the analysis of bisulfite sequencing data from both unique and repetitive sequences http://biochem.jacobs-university.de/BDPC/BISMA/.
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            Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications.

             Ismawati Amin (2009)
            It is well established that invasive urothelial carcinoma, involving the urinary bladder and renal pelvis, has marked propensity for divergent differentiation. In recent years, several 'variant' morphologies have been described and most have been recognized in the 2004 World Health Organization Classification. These histological variants of urothelial carcinoma have clinical significance at various levels, including diagnostic, that is, awareness of the morphological variant is essential in order to avoid diagnostic misinterpretations; prognostic for patient risk stratification; and therapeutic, where a diagnostic assignment of a particular variant may be associated with the administration of a therapy distinctive from that used in conventional invasive urothelial carcinoma. The diagnoses of micropapillary urothelial carcinoma, small-cell carcinoma, lymphoepithelioma-like carcinoma and sarcomatoid carcinoma are prime examples where treatment protocols may be different than the usual muscle-invasive bladder cancer. This review discusses the variants of urothelial carcinoma, outlining for each the diagnostic features, differential diagnostic considerations and the clinical significance.
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              Plasmacytoid urothelial carcinoma, a chemosensitive cancer with poor prognosis, and peritoneal carcinomatosis.

              Plasmacytoid urothelial carcinoma is a rare variant histology with poorly defined clinical behavior. We report clinical outcome information on patients with predominant plasmacytoid urothelial carcinoma.
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                Author and article information

                Journal
                9216904
                2419
                Nat Genet
                Nat. Genet.
                Nature genetics
                1061-4036
                1546-1718
                31 March 2016
                22 February 2016
                April 2016
                01 October 2016
                : 48
                : 4
                : 356-358
                Affiliations
                [1 ]Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
                [2 ]Weill Cornell Medical College, Cornell University, New York, New York, USA
                [3 ]Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
                [4 ]Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
                [5 ]Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan, USA
                [6 ]Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
                [7 ]Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, New York, USA
                [8 ]Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
                [9 ]Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
                [10 ]Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
                Author notes
                Corresponding author: David B. Solit, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. P: 646-888-2641. solitd@ 123456mskcc.org
                [*]

                These authors contributed equally to this manuscript

                Article
                PMC4827439 PMC4827439 4827439 nihpa767649
                10.1038/ng.3503
                4827439
                26901067
                Categories
                Article

                E cadherin, plasmacytoid, bladder cancer, CDH1

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