The Chromosomal Alteration Landscape of Mesothelioma

Malignant pleural mesothelioma (MPM) is a slow growing fatal cancer whose origins begin in the pleural lining of the thoracic cavity. MPM can be classified into three main types of histology, epithelioid, biphasic, and sarcomatoid. Although common mutations have been documented for this pathology such as CDKN2A, TP53, and MDM2, the landscape of alterations to chromosomes and what translocations are present in this cancer has not been fully documented. Here we apply Bionano optical mapping and the rare variant analysis pipeline to 45 separate mesothelioma tumors. We generated a total of 47 trillion bases of molecules maps with an average length of 279.6 kbp. Analysis of the optical mapping with Bionano access software reveled a largely altered chromosomal landscape including whole chromosome translocations, copy number changes and whole chromosome amplifications/deletions. Total events with a deletion threshold greater than 500kp varied greatly across the samples ranging from 1,400 to 2,700 observed events. Hallmark genes observed with large scale complex changes which would have been missed using short read technology include HNF1A,MDM2,ERBB4. This research reveals a highly complex chromosomal landscape for mesothelioma and produces the first global view of complex mutations for this cancer.