Genomics and Epigenetics of Malignant Mesothelioma

Abstract

Malignant mesothelioma is an aggressive and lethal asbestos-related disease. Diagnosis of malignant mesothelioma is particularly challenging and is further complicated by the lack of disease subtype-specific markers. As a result, it is especially difficult to distinguish malignant mesothelioma from benign reactive mesothelial proliferations or reactive fibrosis. Additionally, mesothelioma diagnoses can be confounded by other anatomically related tumors that can invade the pleural or peritoneal cavities, collectively resulting in delayed diagnoses and greatly affecting patient management. High-throughput analyses have uncovered key genomic and epigenomic alterations driving malignant mesothelioma. These molecular features have the potential to better our understanding of malignant mesothelioma biology as well as to improve disease diagnosis and patient prognosis. Genomic approaches have been instrumental in identifying molecular events frequently occurring in mesothelioma. As such, we review the discoveries made using high-throughput technologies, including novel insights obtained from the analysis of the non-coding transcriptome, and the clinical potential of these genetic and epigenetic findings in mesothelioma. Furthermore, we aim to highlight the potential of these technologies in the future clinical applications of the novel molecular features in malignant mesothelioma.

Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation

“…DNA methylation is stable for a long time and miRNAs are particularly resistant to RNase-degradation. Moreover, aberrant peripheral epigenetic modifications have been frequently observed in early-stage cancer patients (38,43,49,50). Thus, circulating epigenetic biomarkers are promising and dynamic markers for early cancer detection, progression, and response to therapy.…”

“…In this context, epigenetic markers such as DNA methylation and microRNAs (miRNAs) are emerging as promising biomarkers for several cancer types, including MPM. While genetic biomarkers may differ from case to case in most cancer patients (i.e., each patient may carry a different mutation within the same gene), different subjects show variable levels of epigenetic biomarkers in a specific target depending on health/disease status (37,38).…”

Zeolites ameliorate asbestos toxicity in a transgenic model of malignant mesothelioma

“…27 The characterization of the genomic and epigenetic landscape of mesothelioma using diverse high-throughput technologies has been reviewed recently. 34 It identified a vast spectrum of coding and non-coding transcriptome changes driving mesothelioma development, but only a fraction of this landscape has been identified by specific mechanistic changes and several of these are common to human cancer development.…”

Panorama epigenético del mesotelioma pleural maligno

“…La incidencia anual del MPM es relativamente baja, estimándose en un rango de 0.6 a 30/1'000,000, pero la ocurrencia global se espera aumente continuamente conforme vayan incrementando más décadas. 1,2 El MPM es extremadamente heterogéneo en su morfología y fenotipos moleculares. El período de latencia para el desarrollo de MPM va 10 a 50 años después de la exposición al asbesto.…”

“…El pronóstico de MPM es casi siempre pobre, con una media de supervivencia de 12 meses desde su diagnóstico. 2,3 La heterogeneidad intratumoral se refiere a una mezcla de diferencias fenotípicas, funcionales y genéticas dentro de las células cancerígenas con varios estatus jerárquicos o de diferenciación dentro de un tumor. Esta heterogeneidad ha sido considerada como el mayor obstáculo en la efectividad de las terapias contra el cáncer, manifestándose en su sensibilidad a las diferentes terapias.…”