Genomic landscape of malignnant mesothelioma by site and histology.

Abstract

8559 Background: Malignnant mesothelioma (MM) is a highly lethal tumor that can develop in the pleura, the peritoneum, the pericardium or the testes. While the genomic features of pleural MM have been well-described overall, less is known about the distribution of genetic alterations (GAs) according to histology. In addition, few reports comparing genetic features according to disease site are available. Methods: We identified patients with pleural or peritoneal mesothelioma with mutational analysis through the GENIE registry. Patient tumor genetic data were provided by Memorial Sloan-Kettering Cancer Center (MSK)-IMPACT and Dana-Farber Cancer Institute (DFCI)-Oncopanel NGS initiatives. Patients with more than one sequenced sample were excluded. We limited our analysis to genes common to all versions of both panels and that were significantly mutated in the TCGA mesothelioma cohort. Mutation and copy number variant (CNV), collectively called GAs, were determined, and were compared using the Fisher’s Exact test and Kruskal-Wallis Test. Comparisons were made both by disease site (pleural vs. peritoneal) and histology for the pleural samples (epithelioid vs. biphasic vs. sarcomatoid). Nominal p-values were obtained, and FDR correction was employed (q<0.1). Results: We identified 439 patients with MM in the GENIE registry who fit the inclusion criteria. The median age was 70.5 years for pleural MM and 60 years for peritoneal MM (Wilcoxon-rank sum test p-value = 3e-9). 72% of patients were male. CDKN2A/CDKN2B GAs (97% and 100% being deletions in CDKN2A and CDKN2B respectively), a described prognostic marker in MM, were more common in pleural than in peritoneal MM. Among pleural MMs, tumors of epithelioid histology had less NF2 GAs than biphasic or sarcomatoid tumors, whereas sarcomatoid tumors had the lowest frequency of BAP1 GAs (Table). Conclusions: Malignnant mesotheliomas of different disease sites and/or histologies display distinct patterns of GAs. These findings may contribute in part to differences in response to treatment and survival among these subsets of MM.[Table: see text]