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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227374/ https://www.ncbi.nlm.nih.gov/pubmed/37260767 http://dx.doi.org/10.1016/j.jbo.2023.100486 |
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author | Suzuki, Rie Wakamatsu, Toru Yoshida, Keiichi Matsuoka, Yukiko Takami, Haruna Nakai, Sho Tamiya, Hironari Kakunaga, Shigeki Yagi, Toshinari Yoshida, Ken-ichi Imura, Yoshinori Yui, Yoshihiro Sasagawa, Satoru Takenaka, Satoshi |
author_facet | Suzuki, Rie Wakamatsu, Toru Yoshida, Keiichi Matsuoka, Yukiko Takami, Haruna Nakai, Sho Tamiya, Hironari Kakunaga, Shigeki Yagi, Toshinari Yoshida, Ken-ichi Imura, Yoshinori Yui, Yoshihiro Sasagawa, Satoru Takenaka, Satoshi |
author_sort | Suzuki, Rie |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10227374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-102273742023-05-31 Genetic characterization of a novel organoid from human malignant giant-cell tumor Suzuki, Rie Wakamatsu, Toru Yoshida, Keiichi Matsuoka, Yukiko Takami, Haruna Nakai, Sho Tamiya, Hironari Kakunaga, Shigeki Yagi, Toshinari Yoshida, Ken-ichi Imura, Yoshinori Yui, Yoshihiro Sasagawa, Satoru Takenaka, Satoshi J Bone Oncol Research Paper 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. Elsevier 2023-05-25 /pmc/articles/PMC10227374/ /pubmed/37260767 http://dx.doi.org/10.1016/j.jbo.2023.100486 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Suzuki, Rie Wakamatsu, Toru Yoshida, Keiichi Matsuoka, Yukiko Takami, Haruna Nakai, Sho Tamiya, Hironari Kakunaga, Shigeki Yagi, Toshinari Yoshida, Ken-ichi Imura, Yoshinori Yui, Yoshihiro Sasagawa, Satoru Takenaka, Satoshi Genetic characterization of a novel organoid from human malignant giant-cell tumor |
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 | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227374/ https://www.ncbi.nlm.nih.gov/pubmed/37260767 http://dx.doi.org/10.1016/j.jbo.2023.100486 |
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