{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:41:16Z","timestamp":1785526876582,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,29]]},"group-title":"Hematology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute"},{"award":["UL1 TR002345"],"award-info":[{"award-number":["UL1 TR002345"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K99 HG007940"],"award-info":[{"award-number":["K99 HG007940"]}],"id":[{"id":"https:\/\/ror.org\/00baak391","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001368","name":"V Foundation for Cancer Research","doi-asserted-by":"crossref","award":["V2018-007"],"award-info":[{"award-number":["V2018-007"]}],"id":[{"id":"10.13039\/100001368","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterized by heterogeneous clinical courses despite a common pathobiological initiating event. In this work we explore the genomic variants that characterize MCL and integrate transcriptomic data to comprehensively describe MCL biology. We performed whole exome sequencing (WES) on 28 tumor-normal pairs (lymph node and skin, respectively), as well as whole genome sequencing (WGS) and RNA sequencing on subsets of samples. We used established DNA and RNA analysis pipelines to detect single-nucleotide variants (SNV) and indels, structural variants, copy-number alterations, and RNA fusions. The canonical t(11;14)(q13;q32)\n                  <jats:italic>CCND1::IGH<\/jats:italic>\n                  translocation was detected in 8 of 10 WGS samples. Structural variant analysis additionally identified recurrent rearrangements involving\n                  <jats:italic>KMT2A<\/jats:italic>\n                  and\n                  <jats:italic>PAFAH1B2<\/jats:italic>\n                  . SNV and indel analyses revealed frequent mutations in\n                  <jats:italic>ATM, TP53, CCND1, IGH<\/jats:italic>\n                  , and\n                  <jats:italic>NOTCH1<\/jats:italic>\n                  .\n                  <jats:italic>ATM<\/jats:italic>\n                  exhibited diverse variant classes, including missense mutations, frameshift mutations, deletions, and duplications, while all detected\n                  <jats:italic>NOTCH1<\/jats:italic>\n                  mutations were predicted loss-of-function frameshift variants. Copy-number analysis identified recurrent losses affecting DNA damage response genes, including\n                  <jats:italic>TP53<\/jats:italic>\n                  and\n                  <jats:italic>ATM<\/jats:italic>\n                  , and recurrent gains involving transcriptional regulators and oncogenic signaling genes. Integrated pathway analysis demonstrated enrichment of transcriptional misregulation, DNA repair,\n                  <jats:italic>PI3K\/AKT<\/jats:italic>\n                  signaling, and interleukin signaling pathways. We also identified recurrent alterations in candidate genes, including\n                  <jats:italic>ASXL1<\/jats:italic>\n                  , suggesting additional mechanisms of epigenetic dysregulation in MCL.\n                <\/jats:p>\n                <jats:p>Together, these findings provide a comprehensive description of somatic alterations in MCL and demonstrate that diverse genomic lesions converge on common pathways involved in genomic instability, transcriptional regulation, and tumor survival.<\/jats:p>","DOI":"10.64898\/2026.07.25.26358867","type":"posted-content","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:00:17Z","timestamp":1785373217000},"source":"Crossref","is-referenced-by-count":0,"title":["Surveying the Genomic Landscape of Mantle Cell Lymphoma Indicates the Importance of Multimodal Genomic and Transcriptomic Exploration"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8568-7193","authenticated-orcid":false,"given":"Charlz Nithin","family":"Jerold","sequence":"first","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Li","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"},{"name":"McDonnell Genome Institute, Department of Medicine, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Mosior","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"},{"name":"McDonnell Genome Institute, Department of Medicine, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Russler-Germain","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"},{"name":"Siteman Cancer Center, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshu","family":"Dahal","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Skidmore","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"},{"name":"McDonnell Genome Institute, Department of Medicine, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-6889","authenticated-orcid":false,"given":"Kelsy C.","family":"Cotto","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"},{"name":"McDonnell Genome Institute, Department of Medicine, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malachi","family":"Griffith","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"},{"name":"McDonnell Genome Institute, Department of Medicine, Washington University School of Medicine, St Louis, MO"},{"name":"Department of Genetics, Washington University School of Medicine, St Louis, MO"},{"name":"Siteman Cancer Center, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Fehniger","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"},{"name":"Siteman Cancer Center, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0843-4271","authenticated-orcid":false,"given":"Obi L.","family":"Griffith","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Medicine, St. Louis, MO 63108"},{"name":"McDonnell Genome Institute, Department of Medicine, Washington University School of Medicine, St Louis, MO"},{"name":"Department of Genetics, Washington University School of Medicine, St Louis, MO"},{"name":"Siteman Cancer Center, Washington University School of Medicine, St Louis, 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