Whole-Genome Comparative Copy Number Alteration Profiling between Malignant Pleural Mesothelioma and Asbestos-Induced Chronic Pleuritis.

Abstract

Malignant pleural mesothelioma (MPM) is rare and aggressive cancer. The most important risk factor for MPM is exposure to asbestos. In this study, we scanned the genomes of individuals MPM and asbestos-induced chronic pleuritis (AICP) to compare and determine copy number alterations (CNAs) between two asbestos-related diseases. We used high-resolution SNP arrays to compare CNA profiles between MPM (n = 55) and AICP (n = 18). DNAs extracted from pleural tissues in both groups. SNP array analysis revealed common losses at 1p, 3p, 6q, 9p, 13q, 14q, 15q, 16q, 22q and frequent gains at chromosomes 1, 3, 5, 7, 8, and 6p, 12q, 15q, 17p, 20q in MPMs (frequencies max 67%-min 30%; these alterations were not detected in AICPs. Besides detecting well-known MPM-associated CNAs, our high -resolution copy number profiling also detected comparatively rare CNAs for MPMs including losses like 9q33.3, 16q and gains of 1p, 1q, 3p, 3q, 6p, 7q, 15q, 12q, 17p, 20q at significant frequencies in the MPM cohort. We also observed Copy Number gains clustered on the NF2 locus in AICPs, whereas this region was commonly deleted in MPMs. According to this distinct genomic profiles between the two groups, AICPs genomes can be clearly distinguished from highly altered MPM genomes. Hence, we can suggest that SNP arrays can be used as a supporting diagnostic tool in terms of discriminating asbestos-related malignant disease such as MPM and benign pleural lesions, which can be challenging in most instances.