Fang W.Wu C.-H.Sun Q.-L.Gu Z.-T.Zhu L.Mao T.Zhang X.-F.Xu N.TZU-PIN LUMONG-HSUN TSAILI-HAN CHENLIANG-CHUAN LAIERIC YAO-YU CHUANG2022-07-282022-07-28202116643224https://www.scopus.com/inward/record.uri?eid=2-s2.0-85120491586&doi=10.3389%2ffimmu.2021.748820&partnerID=40&md5=74cebb3994c139bec2530c59892c27dbhttps://scholars.lib.ntu.edu.tw/handle/123456789/615932Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC. Copyright © 2021 Fang, Wu, Sun, Gu, Zhu, Mao, Zhang, Xu, Lu, Tsai, Chen, Lai and Chuang.driver alteration; gene fusion; immune checkpoint inhibitor (ICI); immunotherapy; neoantigen; RNA sequencing (RNAseq); thymic carcinoma (TC); whole-exome sequencing (WES)biological marker; endogenous compound; HLA antigen; immune checkpoint inhibitor; oligonucleotide; pembrolizumab; programmed death 1 receptor; tumor antigen; ubiquitin carboxyl terminal hydrolase CYLD; transcriptome; tumor antigen; adult; aged; aneuploidy; Article; binding affinity; cancer patient; carcinogenesis; cell proliferation; chromosomal instability; clinical article; controlled study; copy number variation; female; frameshift mutation; gene fusion; gene mutation; gene ontology; human; human tissue; immunogenicity; immunotherapy; indel mutation; male; microsatellite instability; mismatch repair; molecular genetics; multiomics; prevalence; RNA sequencing; somatic mutation; squamous cell lung carcinoma; telomere; thymus cancer; transcriptome sequencing; very elderly; whole exome sequencing; genetics; genomics; immunology; immunotherapy; middle aged; thymoma; Adult; Aged; Antigens, Neoplasm; Carcinogenesis; Female; Genomics; Humans; Immunotherapy; Male; Middle Aged; Thymoma; Thymus Neoplasms; Transcriptomejournal article10.3389/fimmu.2021.748820348679762-s2.0-85120491586