{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T05:49:50Z","timestamp":1791611390122,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":281,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Hepatocellular carcinoma (HCC) is characterized by extensive somatic mutation heterogeneity, yet the cellular contexts in which recurrent driver mutation\u2013associated transcriptional programs operate remain incompletely defined. In this study, we applied a mutation\u2010informed multiomics framework centered on\n                    <jats:italic>TP53<\/jats:italic>\n                    to connect somatic mutation status, bulk transcriptional programs, and hepatocyte\u2010like cell states at single\u2010cell resolution. Somatic mutation profiles and transcriptomic data from the TCGA\u2010LIHC cohort were used to construct directional mutation\u2010associated transcriptional signatures, with\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    retained as a reference driver signature and\n                    <jats:italic>AXIN1<\/jats:italic>\n                    and\n                    <jats:italic>ARID1A<\/jats:italic>\n                    retained for descriptive comparison. These bulk\u2010derived transcriptional programs were then projected into single\u2010cell RNA sequencing data to evaluate inferred\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010associated transcriptional activity across hepatocyte\u2010like populations.\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation\u2010associated transcriptional programs were enriched in proliferation\u2010related pathways, DNA repair processes, and stress\u2013response programs and were associated with adverse clinical outcomes. At the single\u2010cell level, inferred\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010associated transcriptional activity showed heterogeneous distribution across hepatocyte\u2010like populations and was preferentially enriched in putative malignant hepatocyte\u2010like states. Pseudobulk and functional program analyses further supported the association between\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010high signature states, cell\u2010cycle activity, DNA repair, stress programs, and altered tumor\u2010cell communication patterns. Integrated prioritization identified\n                    <jats:italic>CDCA8<\/jats:italic>\n                    ,\n                    <jats:italic>MCM10<\/jats:italic>\n                    , and\n                    <jats:italic>TRIP13<\/jats:italic>\n                    as representative genes associated with\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010related transcriptional programs; these genes should be interpreted as components of a\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010associated proliferative transcriptional state rather than as experimentally validated drivers. These findings provide a mutation\u2010informed view of transcriptional architecture in HCC and illustrate how bulk mutation\u2010associated signatures can be integrated with single\u2010cell data to improve biological interpretation of somatic variation.\n                  <\/jats:p>","DOI":"10.1155\/humu\/2377057","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T05:08:14Z","timestamp":1791608894000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Somatic Mutation\u2013Informed Transcriptional Architecture of Hepatocellular Carcinoma: A Multiomics Study Centered on\n                    <i>TP53<\/i>"],"prefix":"10.1155","volume":"2026","author":[{"given":"Sheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiology Beijing Anzhen Nanchong Hospital of Medical University and Nanchong Central Hospital  Nanchong 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