Genetic characterization of a novel organoid from human malignant giant-cell tumor
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, organoi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Journal of Bone Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137423000192 |
| _version_ | 1797746004278116352 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rie Suzuki |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T15:31:54Z |
| format | Article |
| id | doaj.art-d903d42800474939a0e99b5c544631b2 |
| institution | Directory Open Access Journal |
| issn | 2212-1374 |
| language | English |
| last_indexed | 2024-03-12T15:31:54Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj.art-d903d42800474939a0e99b5c544631b22023-08-10T04:34:13ZengElsevierJournal of Bone Oncology2212-13742023-08-0141100486Genetic characterization of a novel organoid from human malignant giant-cell tumorRie Suzuki0Toru Wakamatsu1Keiichi Yoshida2Yukiko Matsuoka3Haruna Takami4Sho Nakai5Hironari Tamiya6Shigeki Kakunaga7Toshinari Yagi8Ken-ichi Yoshida9Yoshinori Imura10Yoshihiro Yui11Satoru Sasagawa12Satoshi Takenaka13Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Corresponding author at: Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan.Next-generation Precision Medicine Research Center, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, JapanNext-generation Precision Medicine Research Center, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, JapanDepartment of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, JapanDepartment of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, JapanDepartment of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanSarcoma Treatment Laboratory, Research Institute, Nozaki Tokushukai Hospital, Tanigawa 2-10-50, Daito, Osaka 574-0074, JapanMolecular Biology Laboratory, Research Institute, Nozaki Tokushukai Hospital, Tanigawa 2-10-50, Daito, Osaka 574-0074, JapanDepartment of Musculoskeletal Oncology Service, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan; Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanMalignant 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.http://www.sciencedirect.com/science/article/pii/S2212137423000192Malignant giant-cell tumorOrganoidXenograftBone sarcomasH3-3A G34W mutation |
| spellingShingle | 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 Genetic characterization of a novel organoid from human malignant giant-cell tumor Journal of Bone Oncology Malignant giant-cell tumor Organoid Xenograft Bone sarcomas H3-3A G34W mutation |
| title | Genetic characterization of a novel organoid from human malignant giant-cell tumor |
| title_full | Genetic characterization of a novel organoid from human malignant giant-cell tumor |
| title_fullStr | Genetic characterization of a novel organoid from human malignant giant-cell tumor |
| title_full_unstemmed | Genetic characterization of a novel organoid from human malignant giant-cell tumor |
| title_short | Genetic characterization of a novel organoid from human malignant giant-cell tumor |
| title_sort | genetic characterization of a novel organoid from human malignant giant cell tumor |
| topic | Malignant giant-cell tumor Organoid Xenograft Bone sarcomas H3-3A G34W mutation |
| url | http://www.sciencedirect.com/science/article/pii/S2212137423000192 |
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