{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T16:32:27Z","timestamp":1757608347313,"version":"3.44.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>In prostate cancer, it is recognized that adenocarcinoma can transdifferentiate into neuroendocrine prostate cancer (NEPC) owing to lineage plasticity; however, transdifferentiation into other histological types remains uncertain. We present a case of a patient who underwent surgery for adenocarcinoma, which later recurred as prostate carcinosarcoma. Genomic analysis revealed a <jats:italic>TMPRSS2-ERG<\/jats:italic> fusion, confirming a common clonal origin and transdifferentiation from adenocarcinoma to carcinosarcoma. Additionally, we identified a frameshift mutation in <jats:italic>TP53<\/jats:italic> and the loss of <jats:italic>PTEN<\/jats:italic> and <jats:italic>RB1<\/jats:italic>. Transcriptome analysis revealed enriched epithelial-mesenchymal transition and immune-related pathways, a pattern distinct from both adenocarcinoma and NEPC. To our knowledge, this is the first report that comprehensively evaluated the clonal origin of the rare prostate carcinosarcoma and characterized it using genomic and transcriptomic sequencing. It enhances our understanding of prostate cancer lineage plasticity and highlights the importance of developing novel therapies specifically targeted at prostate carcinosarcoma.<\/jats:p>","DOI":"10.3389\/fonc.2025.1576048","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T04:13:20Z","timestamp":1756872800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Genomic insights into prostate adenocarcinoma transdifferentiation to carcinosarcoma due to lineage plasticity"],"prefix":"10.3389","volume":"15","author":[{"given":"Tomohiro","family":"Fukui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arinobu","family":"Fukunaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Teramoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensuke","family":"Hikami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuro","family":"Sunada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Kita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Sumiyoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Goto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoichi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shusuke","family":"Akamatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.6880","article-title":"Clinical and genomic characterization of treatment-emergent small-cell neuroendocrine prostate cancer: A multi-institutional prospective study","volume":"36","author":"Aggarwal","year":"2018","journal-title":"J Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000025237","article-title":"Clinicopathological characteristics and survival outcomes in neuroendocrine prostate cancer: A population-based study","volume":"100","author":"Zhu","year":"2021","journal-title":"Medicine (Baltimore)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/iju.13526","article-title":"Clinical and molecular features of treatment-related neuroendocrine prostate cancer","volume":"25","author":"Akamatsu","year":"2018","journal-title":"Int J Urol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1423","article-title":"The role of lineage plasticity in prostate cancer therapy resistance","volume":"25","author":"Beltran","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3602","DOI":"10.3390\/cancers13143602","article-title":"Lineage plasticity in cancer: The tale of a skin-walker","volume":"13","author":"Thankamony","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1365-2559.2011.04039.x","article-title":"Histological variants of prostatic carcinoma and their significance","volume":"60","author":"Humphrey","year":"2012","journal-title":"Histopathology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0648-8","article-title":"The DNA methylation landscape of advanced prostate cancer","volume":"52","author":"Zhao","year":"2020","journal-title":"Nat Genet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.911410","article-title":"Progress of tumor-associated macrophages in the epithelial-mesenchymal transition of tumor","volume":"12","author":"Li","year":"2022","journal-title":"Front Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1007\/s00018-021-04104-1","article-title":"Integrin-linked kinase (ILK): the known vs. the unknown and perspectives","volume":"79","author":"G\u00f3rska","year":"2022","journal-title":"Cell Mol Life Sci"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3390","DOI":"10.3390\/vaccines11010055","article-title":"Macrophages as a potential immunotherapeutic target in solid cancers","volume":"11","author":"Mishra","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0264138","article-title":"Clinical and analytical validation of FoundationOne\u00aeCDx, a comprehensive genomic profiling assay for solid tumors","volume":"17","author":"Milbury","year":"2022","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nm.4045","article-title":"Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer","volume":"22","author":"Beltran","year":"2016","journal-title":"Nat Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1191311","article-title":"Lineage plasticity and treatment resistance in prostate cancer: the intersection of genetics, epigenetics, and evolution","volume":"14","author":"Imamura","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2008.08074.x","article-title":"Rare and unusual histological variants of prostatic carcinoma: clinical significance","volume":"102","author":"Mazzucchelli","year":"2008","journal-title":"BJU Int"},{"key":"B15","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1111\/his.12493","article-title":"Sarcomatoid carcinoma of the prostate: ERG fluorescence in-situ hybridization confirms epithelial origin","volume":"66","author":"Rodrigues","year":"2015","journal-title":"Histopathology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.7","article-title":"ERG gene rearrangements are common in prostatic small cell carcinomas","volume":"24","author":"Lotan","year":"2011","journal-title":"Mod Pathol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-4012","article-title":"Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule targeting with eribulin","volume":"82","author":"Ho","year":"2022","journal-title":"Cancer Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3336","article-title":"The epigenetics of epithelial-mesenchymal plasticity in cancer","volume":"19","author":"Tam","year":"2013","journal-title":"Nat Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4465","DOI":"10.3390\/cancers14184465","article-title":"Molecular characterizations of gynecologic carcinosarcomas: A focus on the immune microenvironment","volume":"14","author":"Nakad Borrego","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2022-004073","article-title":"Endometrial carcinosarcoma","volume":"33","author":"Bogani","year":"2023","journal-title":"Int J Gynecol Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.3390\/cancers15215294","article-title":"The role of macrophages in sarcoma tumor microenvironment and treatment","volume":"15","author":"Zaj\u0105c","year":"2023","journal-title":"Cancers (Basel)"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1576048\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T04:13:21Z","timestamp":1756872801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1576048\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":21,"alternative-id":["10.3389\/fonc.2025.1576048"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1576048","relation":{},"ISSN":["2234-943X"],"issn-type":[{"type":"electronic","value":"2234-943X"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"article-number":"1576048"}}