The genetic landscape of malignant pleural mesothelioma: results from massively parallel sequencing

Journal of thoracic oncology; official publication of International Association for the Study of Lung Cancer [Epub ahead of print] [Link]

Hylebos M, Van Camp G, van Meerbeeck JP, Op de Beeck K


Malignant pleural mesothelioma (MPM) is a rare yet aggressive tumour, which is causally associated with -mostly professional- asbestos exposure. Given the long latency between exposure and disease, and because asbestos is still being used, MPM will remain a global health issue for decades to come. Notwithstanding the increasing incidence of MPM and the fact that MPM-patients face a poor prognosis, currently available treatment options are limited. To enable the development of novel targeted therapies, identification of the genetic alterations underlying MPM will be crucial. The first studies reporting on the genomic background of MPM identified recurrent somatic mutations in a number of tumour suppressor genes (i.e. CDKN2A, NF2 and BAP1). More recently, massively parallel sequencing strategies have been employed and provided a more genome-wide view on the genetic landscape of MPM. This review summarizes their results, describing alterations that mainly cluster in four pathways: the TP53/DNA-repair-, cell cycle-, MAPK- and PI3K-AKT-pathway. As these pathways are important during tumour development, they provide interesting candidates for targeting with novel drugs.