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      Genomics and Functional Genomics of Malignant Pleural Mesothelioma

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          Abstract

          Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.

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          Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

          The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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            The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics.

            The spindle assembly checkpoint is a safeguard mechanism that coordinates cell-cycle progression during mitosis with the state of chromosome attachment to the mitotic spindle. The checkpoint prevents mitotic cells from exiting mitosis in the presence of unattached or improperly attached chromosomes, thus avoiding whole-chromosome gains or losses and their detrimental effects on cell physiology. Here, I review a considerable body of recent progress in the elucidation of the molecular mechanisms underlying checkpoint signaling, and identify a number of unresolved questions.
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              Transcription factors as targets for cancer therapy.

              A limited list of transcription factors are overactive in most human cancer cells, which makes them targets for the development of anticancer drugs. That they are the most direct and hopeful targets for treating cancer is proposed, and this is supported by the fact that there are many more human oncogenes in signalling pathways than there are oncogenic transcription factors. But how could specific transcription-factor activity be inhibited?
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                01 September 2020
                September 2020
                : 21
                : 17
                : 6342
                Affiliations
                [1 ]Izmir Biomedicine and Genome Center, Izmir 35340, Turkey; ece.cakiroglu@ 123456msfr.ibg.edu.tr
                [2 ]Department of Genome Sciences and Molecular Biotechnology, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey
                Author notes
                Author information
                https://orcid.org/0000-0003-3963-2294
                Article
                ijms-21-06342
                10.3390/ijms21176342
                7504302
                32882916
                48e89b42-df43-435f-ae3c-0e5cd8698af6
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 July 2020
                : 20 August 2020
                Categories
                Review

                Molecular biology
                malignant pleural mesothelioma,genomics,functional genomics,next-generation sequencing,rnai and crispr screens

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