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12.07.2018 | Translational Research and Biomarkers | Ausgabe 9/2018

Annals of Surgical Oncology 9/2018

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

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 9/2018
Autoren:
PhD Mei Gao, BS Miranda Lin, MS Manisha Rao, MD Hannah Thompson, MD Kelsi Hirai, MD Minsig Choi, MD, PhD Georgios V. Georgakis, MD Aaron R. Sasson, MD Juan Carlos Bucobo, MD Demetri Tzimas, MD Lionel S. D’Souza, MD Jonathan M. Buscaglia, MD James Davis, MD, PhD Kenneth R. Shroyer, PhD Jinyu Li, PhD Scott Powers, MD Joseph Kim

Abstract

Background

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.

Methods

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.

Results

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 along with whole-tumor lysates demonstrated absence of tumor heterogeneity. Nested PCR assay identified similar KRAS alterations in primary tumor and paired organoids. Drug sensitivity testing of endoscopic-derived PDOs displayed standard dose–response curves to current gastric cancer cytotoxic therapies.

Conclusions

Our study results demonstrate the feasibility of developing gastric cancer PDOs from EGD biopsies. These results also indicate that endoscopic-derived PDOs are accurate surrogates of the primary tumor and have the potential for drug sensitivity screening and personalized medicine applications.

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