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- W2897816153 abstract "IntroductionMalignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy.MethodsWe used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome.ResultsWe observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient’s circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival.ConclusionsOur findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies." @default.
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- W2897816153 date "2019-02-01" @default.
- W2897816153 modified "2023-09-27" @default.
- W2897816153 title "Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma" @default.
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- W2897816153 doi "https://doi.org/10.1016/j.jtho.2018.10.001" @default.
- W2897816153 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6348045" @default.
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