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Genetics and Epigenetics of Mesothelioma

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Mesothelioma

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Abstract

The definition of the mesothelioma genome is expected to have a great impact toward the development of new drugs and therapeutic approaches with a view to precision medicine. A few studies reported that the malignant pleural mesothelioma (MPM) genomic landscape is characterized by a much greater number of genomic losses than point mutations. Inactivating gene fusions, copy losses, and protein-truncating variants (PTVs) mostly affect tumor suppressor genes, above all BAP1, NF2, CDKN2A, and SETD2. Some of them may be exploited to design novel therapeutic strategies. Germline mutations in some of these genes represent MPM-predisposing risk factors. These mutations require a second hit, i.e., asbestos exposure, to induce carcinogenesis. The most studied of these genes is BAP1. Germline mutations in other tumor suppressor genes, mostly involved in DNA repair, have also been identified in about 10% of MPM patients. These patients are more sensitive to asbestos exposure than those who do not carry such mutations and may benefit of specific treatments. Additionally, epigenetic mechanisms, such as methylation or miRNA alterations, may modify gene expression and drive carcinogenesis. The same abnormalities may be used as disease biomarkers or therapeutic targets.

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Authors and Affiliations

  1. Department of Health Sciences, University of Piemonte Orientale, Novara, Italy

    Anna Aspesi, Marika Sculco & Irma Dianzani

  2. Department of Medical Sciences, University of Turin, Turin, Italy

    Simonetta Guarrera, Elisabetta Casalone & Giuseppe Matullo

  3. Italian Institute for Genomic Medicine, Turin, Italy

    Simonetta Guarrera, Elisabetta Casalone & Giuseppe Matullo

  4. Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy

    Laura Moro

  5. Unit of Cancer Epidemiology, CPO-Piemonte, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy

    Corrado Magnani

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  1. Anna Aspesi
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  1. Department of Medical Oncology, Humanitas Gavazzeni Hospital, Bergamo, Italy

    Giovanni Luca Ceresoli

  2. Scientific Direction, Humanitas Gavazzeni Hospital, Bergamo, Italy

    Emilio Bombardieri

  3. Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy

    Maurizio D'Incalci

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Aspesi, A. et al. (2019). Genetics and Epigenetics of Mesothelioma. In: Ceresoli, G., Bombardieri, E., D'Incalci, M. (eds) Mesothelioma. Springer, Cham. https://doi.org/10.1007/978-3-030-16884-1_4

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