@article{b65acd3aff2448c788d27530451bdb7c,
title = "A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening",
abstract = "Gastric cancer displays marked molecular hetero-geneity 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, tran- scriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term cul- ture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaci- clib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, pro- vides a useful resource for studying both cancer cell biology and precision cancer therapy.",
keywords = "ARHGAP fusions, biobank, drug screening, EBV genome, gastric cancer, heterogeneity, organoid culture, RHOA mutations, transcriptome sequencing, whole-exome sequencing",
author = "Yan, {Helen H.N.} and Siu, {Hoi Cheong} and Simon Law and Ho, {Siu Lun} and Yue, {Sarah S.K.} and Tsui, {Wai Yin} and Dessy Chan and Chan, {April S.} and Stephanie Ma and Lam, {Ka On} and Sina Bartfeld and Man, {Alice H.Y.} and Lee, {Bernard C.H.} and Chan, {Annie S.Y.} and Wong, {Jason W.H.} and Cheng, {Priscilla S.W.} and Chan, {Anthony K.W.} and Jiangwen Zhang and Jue SHI and Xiaodan Fan and Kwong, {Dora L.W.} and Mak, {Tak W.} and Yuen, {Siu Tsan} and Hans Clevers and Leung, {Suet Yi}",
note = "Funding Information: We thank clinicians in the Hong Kong West Cluster, Hospital Authority for clinical care and sample coordination, and H. Wong, H.S. Hui, and H.C. Leung for technical support. We thank the Centre for Genomics Sciences, The University of Hong Kong for performing WES and RNA-seq experiments, and the Core Facility of the LKS Faculty of Medicine HKU for providing imaging and flow cytometry support. We also thank H.E. Francies and M.J. Garnett of Wellcome Trust Sanger Institute for advice on drug screening. This work was substantially supported by a theme-based research grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. T12-710/16-R ), and partly by the Y.W. Kan Endowed Professorship established through a donation from the Croucher Foundation. Equipment support for drug screening was provided by the Jockey Club Centre for Clinical Innovation and Discovery. ",
year = "2018",
month = dec,
day = "6",
doi = "10.1016/j.stem.2018.09.016",
language = "English",
volume = "23",
pages = "882--897, e1--e11",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "6",
}