Whole exome and transcriptome sequencing of tumour cells from malignant mesothelioma pleural effusions. Homo sapiens

Malignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which often contain tumour cells, representing a readily accessible source of tumour cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions is limited. We performed whole exome and transcriptome sequencing of cells from short term cultures of 27 MM pleural effusion samples. Somatic mutations and significant copy number alterations were identified. The mutational landscape observed in MM pleural effusion tumour cells was similar to that reported in solid MM tumours. The median rate of mutations detected in the pleural effusion samples was 1.14 mutations/MB (range 0.38-3.50). We identified significant alteration of CDKN2A (96.3%), BAP1 (70.4%) and NF2 (66.7%). We also identified alterations in SETD2, LATS2, TRAF7 and TP53. Short term cultures of tumour cells from MM pleural effusions contain the same mutations routinely identified in sequencing studies of MM tumour tissue and present novel regions of interest. Cells from pleural effusions will facilitate translational research in MM.