Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations

Abstract

Malignant pleural mesothelioma (MPM) is a clinical emergency of our time. Being strongly associated with asbestos exposure, incidence of this cancer is ramping up these days in many industrialized countries and it will soon start to increase in many developing areas where the use of this silicate derivate is still largely in use. Deficiency of reliable markers for the early identification of these tumors and the limited efficacy of the currently available therapeutic options are the basis of the impressive mortality rate of MPM. These shortcomings reflect the very poor information available about the molecular basis of this disease. Results of the recently released deep profiling studies point to the epigenome as a central element in MPM development and progression. First, MPM is characterized by a low mutational burden and a highly peculiar set of mutations that hits almost exclusively epigenetic keepers or proteins controlling chromatin organization and function. Furthermore, asbestos does not seem to be associated with a distinctive mutational signature, while the precise mapping of epigenetic changes caused by this carcinogen has been defined, suggesting that alterations in epigenetic features are the driving force in the development of this disease. Last but not least, consistent evidence also indicates that, in the setting of MPM, chromatin rewiring and epigenetic alterations of cancer cells heavily condition the microenvironment, including the immune response. In this review we aim to point to the relevance of the epigenome in MPM and to highlight the dependency of this tumor on chromatin organization and function. We also intend to discuss the opportunity of targeting these mechanisms as potential therapeutic options for MPM.

Exaggerated Risk Perception of Low-Dose Exposures to Asbestos: Cui Bono?

“…Chromosomal aberrations in MPM are heterogenous [16,33]. The information on the molecular basis of MPM is insufficient [34]. According to the Helsinki Criteria, established for attribution of mesothelioma to asbestos, no specific recommendations can be given for the use of markers in the screening for MPM [35,36].…”

Asbestos-Related Diseases and Policies: an Update

“…Chromosomal and genomic aberrations of MPM are heterogenous [15,45,46]. Available information about the molecular basis of MPM is insufficient [47]. According to the Helsinki Criteria, established for attribution of mesothelioma to asbestos, no specific recommendations can be given for the use of markers in the screening for MPM [48,49].…”

Asbestos and anti-asbestos activism: medical and economical aspects

“…Chromosomal aberrations of MPM are heterogenous (Lindholm et al 2007;Musti et al 2006;Røe et al 2009). Available information about the molecular basis of MPM is insufficient (Lorenzini et al 2021). According to the Helsinki Criteria, established for attribution of mesothelioma to asbestos, no specific recommendations can be given for the use of markers in the screening for MPM (Ferrari et al 2020;Wolff et al 2015).…”