A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

TY - JOUR

T1 - A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

AU - Yan, Helen H N

AU - Siu, Hoi Cheong

AU - Law, Simon

AU - Ho, Siu Lun

AU - Yue, Sarah S K

AU - Tsui, Wai Yin

AU - Chan, Dessy

AU - Chan, April S

AU - Ma, Stephanie

AU - Lam, Ka On

AU - Bartfeld, Sina

AU - Man, Alice H Y

AU - Lee, Bernard C H

AU - Chan, Annie S Y

AU - Wong, Jason W H

AU - Cheng, Priscilla S W

AU - Chan, Anthony K W

AU - Zhang, Jiangwen

AU - Shi, Jue

AU - Fan, Xiaodan

AU - Kwong, Dora L W

AU - Mak, Tak W

AU - Yuen, Siu Tsan

AU - Clevers, Hans

AU - Leung, Suet Yi

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/12/6

Y1 - 2018/12/6

N2 - Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.

AB - Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.

U2 - 10.1016/j.stem.2018.09.016

DO - 10.1016/j.stem.2018.09.016

M3 - Article

C2 - 30344100

SN - 1934-5909

VL - 23

SP - 882-897.e11

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 6

ER -