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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
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.
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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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