Aaron S. Mansfield, MD, Tobias Peikert, MD, James B

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Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma Aaron S. Mansfield, MD, Tobias Peikert, MD, James B. Smadbeck, PhD, Julia B.M. Udell, MA, Enrique Garcia-Rivera, PhD, Laura Elsbernd, BS, Courtney L. Erskine, BS, Virginia P. Van Keulen, MS, Farhad Kosari, PhD, Stephen J. Murphy, PhD, Hongzheng Ren, MD, PhD, Vishnu V. Serla, MBBS, Janet L. Schaefer Klein, MA, Giannoula Karagouga, MS, Faye R. Harris, MS, Carlos Sosa, PhD, Sarah H. Johnson, MS, Wendy Nevala, MS, Svetomir N. Markovic, MD, PhD, Aaron O. Bungum, BS, Eric S. Edell, MD, Haidong Dong, MD, PhD, John C. Cheville, MD, Marie Christine Aubry, MD, Jin Jen, MD, PhD, George Vasmatzis, PhD Journal of Thoracic Oncology Volume 14, Issue 2, Pages 276-287 (February 2019) DOI: 10.1016/j.jtho.2018.10.001 Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Genomic event summary. The unfilled circles represent the number of mate-pair sequencing–detected junctions (rearrangements), the black circles represent the number rearrangements involving genes, and the green circles represent the number of peptides that are potential neoantigens. Journal of Thoracic Oncology 2019 14, 276-287DOI: (10.1016/j.jtho.2018.10.001) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Genome plot for ME022. In this genome plot of specimen ME022 the chromosomes are plotted in order by size as numbered near the margins. Curved pink lines represent intrachromosomal rearrangements wheres light green lines represent interchromosomal rearrangements. Deletions are represented in red and amplifications are represented in blue. Accordingly, the multiple pink lines on chromosome 7 represent chromothripsis and the green lines between chromosomes 7 and 11 represent chromoplexy. CNV, copy number variation. Journal of Thoracic Oncology 2019 14, 276-287DOI: (10.1016/j.jtho.2018.10.001) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Validation of CADPS2 rearrangement in ME018. The junction plot in the top left presents the mate-pair reads supporting the intrachromosomal rearrangement between CADPS2 and a nongenic region on chromosome 7. Red and blue dots represent mate-pair reads mapping to the positive or negative DNA strands, respectively, with coverage levels across each position presented in gray-shaded regions, with single (1N) and two-copy levels (2N) indicated (green). Gene regions are presented in red with exons numerated. On the top right of this figure, this rearrangement was confirmed by polymerase chain reaction with primers spanning the breakpoint in both DNA and RNA in ME018, but not in negative controls (pooled human genomic DNA for DNA validation, and case ME025 which lacked this rearrangement for RNA validation). In the bottom of this figure, this rearrangement was confirmed by Sanger sequencing of the DNA. Journal of Thoracic Oncology 2019 14, 276-287DOI: (10.1016/j.jtho.2018.10.001) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Kaplan-Meier survival curve for mesothelioma by chromothripsis-like pattern (CTLP) detection. Subjects were classified by the presence of 0 to 2 CTLPs (n = 64), or 3 or more CTLPs (3+; n = 23). Survival was significantly worse for patients with 3+ CTLPs (hazard ratio: 2.002, p = 0.006). Journal of Thoracic Oncology 2019 14, 276-287DOI: (10.1016/j.jtho.2018.10.001) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions