{"doi":"10.1101/2021.08.01.21260883","title":"Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma","abstract":"Abstract Background Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy. Methods In order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a young female never-smoker with late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T-cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors. Results We observed heterogeneous mutation, methylation, and T cell patterns across distinct metastases including a set of prevalent T cell clonotypes which were completely excluded from left-side thoracic tumors. Though a limited number of predicted neoantigens were shared, these were associated with homology of the T cell repertoire across metastases. Lastly, ratio of methylated neoantigen coding mutations was negatively associated with T-cell density, richness and clonality, suggesting neoantigen methylation may partially drive immunosuppression. Conclusions Our study demonstrates heterogeneous genomic and T cell profiles across synchronous metastases and how restriction of unique T cell clonotypes within an individual may differentially shape the genomic and epigenomic landscapes of synchronous lung metastases.","journal":"medRxiv","year":2021,"id":229518,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9335,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":317293,"name":"Jun Li","orcid":"0000-0002-1171-7141","position":1,"is_corresponding":false},{"id":69930,"name":"Junya Fujimoto","orcid":"0000-0003-4813-3163","position":2,"is_corresponding":false},{"id":620410,"name":"Xin Hu","orcid":"0000-0002-5105-8929","position":3,"is_corresponding":false},{"id":828760,"name":"Kelly Quek","orcid":"0000-0002-8113-0944","position":4,"is_corresponding":false},{"id":12217,"name":"Ming Tang","orcid":"0000-0002-7739-8913","position":5,"is_corresponding":false},{"id":828761,"name":"Akash Mitra","orcid":"0000-0002-0633-1615","position":6,"is_corresponding":false},{"id":69926,"name":"Carmen Behrens","orcid":"0000-0003-1905-8061","position":7,"is_corresponding":false},{"id":589216,"name":"Chi-Wan Chow","orcid":null,"position":8,"is_corresponding":false},{"id":438353,"name":"Peixin Jiang","orcid":"0000-0002-9249-7813","position":9,"is_corresponding":false},{"id":230398,"name":"Latasha Little","orcid":"0000-0001-9690-6314","position":10,"is_corresponding":false},{"id":230399,"name":"Curtis Gumbs","orcid":"0000-0001-8026-0897","position":11,"is_corresponding":false},{"id":230401,"name":"Xingzhi Song","orcid":"0000-0002-9436-2728","position":12,"is_corresponding":false},{"id":230400,"name":"Jianhua Zhang","orcid":"0000-0001-5412-9860","position":13,"is_corresponding":false},{"id":829058,"name":"Dongfeng Tan","orcid":null,"position":15,"is_corresponding":false},{"id":227923,"name":"John V. 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