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Consequently, its pathogenesis remains largely unknown, with no cell lines established from primary tumors. Here, we report the first establishment of<jats:styled-content style=\"fixed-case\">cCCC<\/jats:styled-content>organoids, from biopsy samples of a 23\u2010year\u2010old patient diagnosed with<jats:styled-content style=\"fixed-case\">cCCC<\/jats:styled-content>. By applying a protocol that we recently optimized for gynecological tumors, we were able to propagate a patient\u2010derived cell line (<jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>) for more than 6\u00a0months as organoids. This<jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>tolerated cryopreservation and proliferated either as spheroids or adherent cells, and developed xenografts in immunodeficient mice, ensuring robust utility as a cell line. Intriguingly, the resected tumor focally contained serous carcinoma (<jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>) in a tiny protruding lesion. Both organoids and derivative xenografts resembled the<jats:styled-content style=\"fixed-case\">CCC<\/jats:styled-content>component of the original tumor in histology, immunostaining profile, and genome\u2010wide copy number changes, including focal gain of<jats:italic><jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content><\/jats:italic>. Genomic analysis revealed that both organoids and the<jats:styled-content style=\"fixed-case\">CCC<\/jats:styled-content>component harbored only a few mutations, of which 2 mutations were shared in common. In contrast, the<jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>component showed a mutator\u2010phenotype and prominent genome instability along with biallelic inactivation of<jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic>, but none of them were found in organoids or the<jats:styled-content style=\"fixed-case\">CCC<\/jats:styled-content>component. The<jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>proved sensitive to major chemotherapeutic agents and<jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content>inhibitors. These observations clearly indicated that the<jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>, designated as<jats:styled-content style=\"fixed-case\">YMC<\/jats:styled-content>7, can be used as a novel<jats:styled-content style=\"fixed-case\">cCCC<\/jats:styled-content>cell line and provide novel insights into the pathogenesis of mixed cervical adenocarcinoma. As a valuable resource for rare cancer, it will likely contribute to investigations in many fields.<\/jats:p>","DOI":"10.1111\/cas.14119","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T09:55:16Z","timestamp":1562061316000},"page":"2992-3005","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Establishment and characterization of patient\u2010derived organoids from a young patient with cervical clear cell carcinoma"],"prefix":"10.1111","volume":"110","author":[{"given":"Yoshiaki","family":"Maru","sequence":"first","affiliation":[{"name":"Department of Molecular Carcinogenesis Chiba Cancer Center Research Institute Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotake","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gynecology Chiba Cancer Center Chiba 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