ABSTRACT
Malignant mesothelioma (MM) is a tumor of adult life that mostly affects individuals older than 50 years of age and occurs more commonly in men than in women.1
Approximately 3000 patients are diagnosed with MM in the USA each year. MMs arise from serosal surfaces and are approximately four times more common in the pleural than in the peritoneal cavity. MM manifests as a diffuse or localized growth, with the former accounting for approximately 75 percent of all cases.1 The increasing frequency of this disease over the last 40 years is a reflection of exposure to asbestos fibers in industrialized countries, particularly in connection with the mining and shipyard industries.2 A history of asbestos exposure is associated with approximately 80 percent of the cases, and a lag phase of 20-40 years between exposure and tumor development is usual. In pleural MM, the first symptoms are typically dyspnea and chest pain, and radiological examination often reveals a pleural effusion. Cytological discrimination between MM, benign inflammatory or reactive effusions, and metastatic carcinoma is not always clear.1 On the other hand, recurrent cytogenetic and molecular genetic abnormalities have been identified in MM, which can aid in discriminating neoplastic disease from benign mesothelioma. Besides asbestos, some evidence has implicated Simian virus 40 (SV40) in the etiology of some MMs.3,4 (See also Chapter 41, Malignant mesothelioma.)
In this chapter, we provide an overview of both cytogenetic and molecular genetic alterations in MM, mechanisms by which asbestos and other carcinogenic mineral fibers contribute to MM pathogenesis, and briefly discuss potential signaling pathways by which alterations of
multistep tumorigenic process. We also discuss potential therapeutic approaches that target molecular alterations found in this disease.
