Cell Signaling and Epigenetic Mechanisms in Mesothelioma

Abstract

Malignant mesotheliomas are a histologically diverse, polyclonal group of tumors arising most commonly in the pleura and to a lesser extent in the peritoneum, pericardium, and tunica vaginalis testis. They are primarily associated with exposures to naturally occurring mineral fibers including asbestos, erionite, and fluoro-edenite, although radiation- and chronic inflammation-associated as well as idiopathic mesotheliomas occur. Integrated analyses of pleural mesotheliomas have shown heterogeneous mutations in tumor suppressor genes, stimulation of multiple signaling cascades and transcription factors, and, most recently, epigenetic alterations that are defined as heritable and/or reversible changes in gene expression without changes in the DNA sequence. This review focuses on the epigenetic mechanisms reported in studies on mesotheliomas and mesothelial cells, emphasizing research that has linked these changes to critical survival and proliferative pathways in the development of mesotheliomas. This information is critical to understanding how key epigenetic effects modulate the carcinogenic process and will allow new strategies to prevent and treat mesotheliomas.