دورية أكاديمية
Genetic characterization of a novel organoid from human malignant giant-cell tumor
العنوان: | Genetic characterization of a novel organoid from human malignant giant-cell tumor |
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المؤلفون: | Rie Suzuki, Toru Wakamatsu, Keiichi Yoshida, Yukiko Matsuoka, Haruna Takami, Sho Nakai, Hironari Tamiya, Shigeki Kakunaga, Toshinari Yagi, Ken-ichi Yoshida, Yoshinori Imura, Yoshihiro Yui, Satoru Sasagawa, Satoshi Takenaka |
المصدر: | Journal of Bone Oncology, Vol 41, Iss , Pp 100486- (2023) |
بيانات النشر: | Elsevier, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Diseases of the musculoskeletal system LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
مصطلحات موضوعية: | Malignant giant-cell tumor, Organoid, Xenograft, Bone sarcomas, H3-3A G34W mutation, Diseases of the musculoskeletal system, RC925-935, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
الوصف: | Malignant giant-cell tumors are extremely rare bone sarcomas that transform from conventional giant-cell tumors during long periods of treatment. Owing to their rarity, no further analysis of their molecular pathogenesis exists, and thus, no standard treatment has been established. Recently, organoid culture methods have been highlighted for recapturing the tumor microenvironment, and we have applied the culture methods and succeeded in establishing patient-derived organoids (PDO) of rare sarcomas. This study aimed to investigate the genomic characteristics of our established novel organoids from human malignant giant-cell tumors. At our institute, we treated a patient with malignant giant-cell tumor. The remaining sarcoma specimens after surgical resection were cultured according to the air–liquid interface organoid-culture method. Organoids were xenografted into NOD-scid IL2Rgnull mice. The developed tumors were histologically and genomically analyzed to compare their characteristics with those of the original tumors. Genetic changes over time throughout treatment were analyzed, and the genomic status of the established organoid was confirmed. Organoids from malignant giant-cell tumors could be serially maintained using air–liquid interface organoid-culture methods. The tumors developed in xenografted NOD-scid IL2Rgnull mice. After several repetitions of the process, a patient-derived organoid line from the malignant giant-cell tumor was established. Immunohistochemical analyses and next-generation sequencing revealed that the established organoids lacked the H3-3A G34W mutation. The xenografted organoids of the malignant giant-cell tumor had phenotypes histologically and genetically similar to those of the original tumor. The established organoids were confirmed to be derived from human malignant giant-cell tumors. In summary, the present study demonstrated a novel organoid model of a malignant giant-cell tumor that was genetically confirmed to be a malignant transformed tumor. Our organoid model could be used to elucidate the molecular pathogenesis of a malignant giant-cell tumor and develop novel treatment modalities. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2212-1374 |
Relation: | http://www.sciencedirect.com/science/article/pii/S2212137423000192; https://doaj.org/toc/2212-1374 |
DOI: | 10.1016/j.jbo.2023.100486 |
URL الوصول: | https://doaj.org/article/d903d42800474939a0e99b5c544631b2 |
رقم الأكسشن: | edsdoj.903d42800474939a0e99b5c544631b2 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 22121374 |
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DOI: | 10.1016/j.jbo.2023.100486 |