Abstract：
Malignant pleural mesothelioma (MPM) is a rare type of cancer, and its main risk factor is exposure to asbestos. Accordingly, our knowledge of the genomic structure of an MPM tumor is limited when compared to other cancers. In this study, we aimed to characterize complex genomic rearrangement patterns and variations to better understand the genomics of MPM tumors. We comparatively scanned 3 MPM tumor genomes by Whole-Genome Sequencing and High-Resolution SNP array. We also used various computational algorithms to detect both CNAs and complex chromosomal rearrangements. Genomic data obtained from each bioinformatics tool are interpreted comparatively to better understand CNAs and cancer-related Nucleotide variations in MPM tumors. In patients 1 and 2, we found pathogenic nucleotide variants of BAP1, RB1, and TP53. These two MPM genomes exhibited a highly rearranged chromosomal rearrangement pattern resembling Chromomanagesis particularly in the form of Chromoanasynthesis. In patient 3, we found nucleotide variants of important cancer-related genes, including TGFBR1, KMT2C, and PALLD, to have lower chromosomal rearrangement complexity compared with patients 1 and 2. We also detected several actionable nucleotide variants including XRCC1, ERCC2. We also discovered the SKA3-DDX10 fusion in two MPM genomes, which is a novel finding for MPM. We found that MPM genomes are very complex, suggesting that this highly rearranged pattern is strongly related to driver mutational status like BAP1, TP53 and RB1.
摘要：
恶性胸膜间皮瘤（MPM）是一种罕见的癌症，其主要危险因素是接触石棉。因此，与其他癌症相比,我们对MPM肿瘤基因组结构的了解有限.在这项研究中,我们旨在表征复杂的基因组重排模式和变异,以更好地理解MPM肿瘤的基因组学.我们通过全基因组测序和高分辨率SNP阵列比较扫描了3个MPM肿瘤基因组。我们还使用各种计算算法来检测CNA和复杂的染色体重排。比较地解释从每个生物信息学工具获得的基因组数据,以更好地理解MPM肿瘤中的CNA和癌症相关核苷酸变异。在患者1和2中，我们发现了BAP1，RB1和TP53的致病性核苷酸变体。这两个MPM基因组表现出高度重排的染色体重排模式，类似于染色体发生，特别是以染色体异步形式。在患者3中，我们发现了重要的癌症相关基因的核苷酸变异，包括TGFBR1，KMT2C，苍白，与患者1和2相比，具有较低的染色体重排复杂性。我们还检测到几种可操作的核苷酸变体，包括XRCC1，ERCC2。我们还在两个MPM基因组中发现了SKA3-DDX10融合体，这是MPM的一个新发现。我们发现MPM基因组非常复杂，表明这种高度重排的模式与驾驶员突变状态如BAP1，TP53和RB1密切相关。
