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

          Christian Rohde, Yingying Zhang, Richard Reinhardt … (2010)
          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.

            Mahul B 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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              Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer.

              Brian Chin, Jonathan I Izawa, Venu Chalasani (2009)
              Bladder cancer can be classified histologically as urothelial or non-urothelial. Urothelial cancer has a propensity for divergent differentiation, which has increasingly been recognized in recent years due to heightened awareness and improved immunohistochemistry techniques. Furthermore, the recent World Health Organization classification of urothelial cancers improved clarity on this issue, with its listing of 13 histologic variants of urothelial cancer. The divergent differentiation patterns include, amongst others, squamous, glandular, micropapillary, nested, lymphepithelioma-like, plasmacytoid and sarcomatoid variants of urothelial cancer. Attempts to quantify the amount of divergent differentiation present, such as using the nonconventional differentiation number, have been made recently, which will improve the ability to compare publications from different centres. Genetic-based studies have indicated that the histologic variants of urothelial cancer arise from a common clonal precursor. Mostly, the current evidence suggests that urothelial cancer with divergent differentiation has a worse prognosis when compared with pure urothelial cancer. This article will review the current literature on variant histologies of urothelial cancer, and well as new developments in pure squamous cell carcinoma, small cell carcinoma and adenocarcinoma of the bladder.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Nat. Genet.
                Title: Nature genetics
                ISSN: 1061-4036
                ISSN (Print): 1061-4036
                Publication date (Electronic): Apr 2016
                Volume: 48
                Issue: 4
                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.
                Article
                Publisher Item ID: ng.3503 Mid ID: NIHMS767649
                DOI: 10.1038/ng.3503
                PMC ID: 4827439
                PubMed ID: 26901067
                SO-VID: e26142e4-bc5d-483c-b47d-3e3487012a25
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