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Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report

The gastrointestinal stromal tumors (GIST) are a rare gastrointestinal tract malignancy. The two primary mutation sites are found in KIT and platelet-derived growth factor receptor-α (PDGFR-α) genes. The current study reports on a point mutation within the exon 11 of KIT, named KIT p.V560E. Patient-...

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Autores principales: Cao, Ying, Zhang, Xi, Chen, Qianyun, Rao, Xi, Qiu, Enming, Wu, Gang, Lin, Yu, Zeng, Ziqi, Zheng, Bin, Li, Zhou, Cai, Zhai, Wang, Huaiming, Han, Shuai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378866/
https://www.ncbi.nlm.nih.gov/pubmed/35982969
http://dx.doi.org/10.3389/fonc.2022.920762
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author Cao, Ying
Zhang, Xi
Chen, Qianyun
Rao, Xi
Qiu, Enming
Wu, Gang
Lin, Yu
Zeng, Ziqi
Zheng, Bin
Li, Zhou
Cai, Zhai
Wang, Huaiming
Han, Shuai
author_facet Cao, Ying
Zhang, Xi
Chen, Qianyun
Rao, Xi
Qiu, Enming
Wu, Gang
Lin, Yu
Zeng, Ziqi
Zheng, Bin
Li, Zhou
Cai, Zhai
Wang, Huaiming
Han, Shuai
author_sort Cao, Ying
collection PubMed
description The gastrointestinal stromal tumors (GIST) are a rare gastrointestinal tract malignancy. The two primary mutation sites are found in KIT and platelet-derived growth factor receptor-α (PDGFR-α) genes. The current study reports on a point mutation within the exon 11 of KIT, named KIT p.V560E. Patient-derived organoids (PDOs) are potential 3D in vitro models of tissues that can be used to identify sensitivity toward specific targets in patients with tumors and allow for personalized medicine when drugs specific for newly identified genetic locus mutations are not yet available. This study describes a 68-year-old patient who complained of diffused abdominal pain and intermittent melena lasting more than 10 days. He has no other gastrointestinal abnormalities, prior abdominal surgery, or related family history. Surgery was conducted first to remove the lesions and ascertain the disease through histology and immunohistochemical stains of the mass. Immunohistochemistry revealed that the tumor was positive for CD117 and Dog-1. Based on the above findings, he was diagnosed with GISTs. Gene detection analysis and organoid culture were then performed to verify clinical decisions. KIT p.V560E and the reduced number of RB1 copies were identified as two obvious mutations, so the patient was administrated first-line treatment of imatinib 400 mg/d. However, progressive disease prompted us to switch to sunitinib, and his condition gradually improved. Meanwhile, organoid culture showed sensitivity to sunitinib and tolerance to imatinib with half-maximal inhibitory concentration (IC50) values of 0.89 and >20, respectively. In summary, to the best of our knowledge, this is the first time that the established organoid culture indicated that the GISTs organoid could identify the sensitivity to target therapies and facilitate individual-based treatment.
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spelling pubmed-93788662022-08-17 Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report Cao, Ying Zhang, Xi Chen, Qianyun Rao, Xi Qiu, Enming Wu, Gang Lin, Yu Zeng, Ziqi Zheng, Bin Li, Zhou Cai, Zhai Wang, Huaiming Han, Shuai Front Oncol Oncology The gastrointestinal stromal tumors (GIST) are a rare gastrointestinal tract malignancy. The two primary mutation sites are found in KIT and platelet-derived growth factor receptor-α (PDGFR-α) genes. The current study reports on a point mutation within the exon 11 of KIT, named KIT p.V560E. Patient-derived organoids (PDOs) are potential 3D in vitro models of tissues that can be used to identify sensitivity toward specific targets in patients with tumors and allow for personalized medicine when drugs specific for newly identified genetic locus mutations are not yet available. This study describes a 68-year-old patient who complained of diffused abdominal pain and intermittent melena lasting more than 10 days. He has no other gastrointestinal abnormalities, prior abdominal surgery, or related family history. Surgery was conducted first to remove the lesions and ascertain the disease through histology and immunohistochemical stains of the mass. Immunohistochemistry revealed that the tumor was positive for CD117 and Dog-1. Based on the above findings, he was diagnosed with GISTs. Gene detection analysis and organoid culture were then performed to verify clinical decisions. KIT p.V560E and the reduced number of RB1 copies were identified as two obvious mutations, so the patient was administrated first-line treatment of imatinib 400 mg/d. However, progressive disease prompted us to switch to sunitinib, and his condition gradually improved. Meanwhile, organoid culture showed sensitivity to sunitinib and tolerance to imatinib with half-maximal inhibitory concentration (IC50) values of 0.89 and >20, respectively. In summary, to the best of our knowledge, this is the first time that the established organoid culture indicated that the GISTs organoid could identify the sensitivity to target therapies and facilitate individual-based treatment. Frontiers Media S.A. 2022-08-02 /pmc/articles/PMC9378866/ /pubmed/35982969 http://dx.doi.org/10.3389/fonc.2022.920762 Text en Copyright © 2022 Cao, Zhang, Chen, Rao, Qiu, Wu, Lin, Zeng, Zheng, Li, Cai, Wang and Han https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Cao, Ying
Zhang, Xi
Chen, Qianyun
Rao, Xi
Qiu, Enming
Wu, Gang
Lin, Yu
Zeng, Ziqi
Zheng, Bin
Li, Zhou
Cai, Zhai
Wang, Huaiming
Han, Shuai
Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report
title Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report
title_full Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report
title_fullStr Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report
title_full_unstemmed Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report
title_short Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report
title_sort patient-derived organoid facilitating personalized medicine in gastrointestinal stromal tumor with liver metastasis: a case report
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378866/
https://www.ncbi.nlm.nih.gov/pubmed/35982969
http://dx.doi.org/10.3389/fonc.2022.920762
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