Establishment and characterization of patient‐derived organoids from a young patient with cervical clear cell carcinoma. Issue 9 (23rd July 2019)

• Record Type: Journal Article
• Authors: Maru, Yoshiaki; Tanaka, Naotake; Ebisawa, Keiko; Odaka, Akiko; Sugiyama, Takahiro; Itami, Makiko; Hippo, Yoshitaka
• Is Part Of: Cancer science. Volume 110:Issue 9(2019)
• Page Start: 2992
• Page End: 3005
• Publication Date: 2019-07-23
• Subjects: cervical cancer -- clear cell carcinoma -- organoid -- patient‐derived cell -- preclinical model; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14119
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Cervical clear cell carcinoma (cCCC) constitutes an extremely rare subtype of cervical cancer. Consequently, its pathogenesis remains largely unknown, with no cell lines established from primary tumors. Here, we report the first establishment of cCCC organoids, from biopsy samples of a 23‐year‐old patient diagnosed with cCCC. By applying a protocol that we recently optimized for gynecological tumors, we were able to propagate a patient‐derived cell line (PDC) for more than 6 months as organoids. This PDC 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 (SC) in a tiny protruding lesion. Both organoids and derivative xenografts resembled the CCC component of the original tumor in histology, immunostaining profile, and genome‐wide copy number changes, including focal gain of MET . Genomic analysis revealed that both organoids and the CCC component harbored only a few mutations, of which 2 mutations were shared in common. In contrast, the SC component showed a mutator‐phenotype and prominent genome instability along with biallelic inactivation of TP53, but none of them were found in organoids or the CCC component. The PDC proved sensitive to major chemotherapeutic agents and MET inhibitors. These observations clearly indicated that the PDC, designated as YMC7, can be used as a novel cCCC 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. Abstract : Using an organoid culture technique, the YMC7 cell line was established for the first time from the biopsy samples of primary cervical clear cell carcinoma, a rare subtype of cervical cancer. YMC7 retained many features of the clear cell carcinoma component of the tumor, but not the serous carcinoma component, providing insights into the pathogenesis of cervical adenocarcinoma. YMC7 gave rise to spheroids, adherent cells, and xenografts, potentially facilitating screening for drug discovery, and will likely serve as a valuable model for cervical clear cell carcinoma.