Development of Patient-Derived Gastric Cancer Organoids from Endoscopic Biopsies and Surgical Tissues

Annals of Surgical Oncology
Mei GaoJoseph Kim

Abstract

Organoids are three-dimensional in vitro models of human disease developed from benign and malignant gastrointestinal tissues with tremendous potential for personalized medicine applications. We sought to determine whether gastric cancer patient-derived organoids (PDOs) could be safely established from endoscopic biopsies for rapid drug screening. Patients underwent esophagogastroduodenoscopy (EGD) for surveillance or staging and had additional forceps biopsies taken for PDO creation. Cancer tissues from operative specimens were also used to create PDOs. To address potential tumor heterogeneity, we performed low-coverage whole-genome sequencing of endoscopic-derived PDOs with paired surgical PDOs and whole-tumor lysates. The stability of genomic alterations in endoscopic organoids was assessed by next-generation sequencing and nested polymerase chain reaction (PCR) assay. The feasibility and potential accuracy of drug sensitivity screening with endoscopic-derived PDOs were also evaluated. Gastric cancer PDOs (n = 15) were successfully established from EGD forceps biopsies (n = 8) and surgical tissues (n = 7) from five patients with gastric adenocarcinoma. Low-coverage whole-genomic profiling of paired EGD and surgical PDOs alon...Continue Reading

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Citations

Feb 27, 2020·Nature Reviews. Gastroenterology & Hepatology·Harry Cheuk Hay LauJun Yu
Oct 3, 2020·Cancers·George AlzeebCatherine Le Jossic-Corcos
Sep 13, 2018·International Journal of Molecular Sciences·Giuseppe TirinoFerdinando De Vita
Oct 11, 2019·Journal of Gastric Cancer·Jaewook Jeon, Jae-Ho Cheong
Jan 23, 2020·World Journal of Gastrointestinal Oncology·Tasuku Matsuoka, Masakazu Yashiro
Jul 31, 2020·British Journal of Cancer·Ross J PorterMairi H McLean
Nov 28, 2019·Animal Models and Experimental Medicine·Lauren M GranatDong Zhang
Aug 2, 2019·World Journal of Gastrointestinal Oncology·Miranda LinJoseph Kim
Jul 12, 2020·Journal of Molecular Cell Biology·Ramon U Jin, Jason C Mills
Sep 16, 2020·Nature Protocols·Else DriehuisHans Clevers
Apr 6, 2021·Frontiers in Oncology·Maikel VerduinMarc Vooijs
Oct 16, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Kai Kretzschmar
Aug 3, 2021·Journal of Tissue Engineering and Regenerative Medicine·Letícia E CharelliTiago A Balbino
Sep 29, 2021·Molecular Pharmaceutics·Fengjiao LiZhonghua Liu
Sep 22, 2021·Cellular and Molecular Gastroenterology and Hepatology·Min-Jiao PangZhen-Ning Wang

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