File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)

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

TitleA Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening
Authors
KeywordsARHGAP fusions
Biobank
Drug screening
EBV genome
Gastric cancer
Heterogeneity
Organoid culture
RHOA mutations
Transcriptome sequencing
Whole-exome sequencing
Issue Date2018
PublisherCell Press. The Journal's web site is located at http://www.cellstemcell.com
Citation
Cell Stem Cell, 2018, v. 23 n. 6, p. 882-897.e11 How to Cite?
AbstractGastric 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.
Persistent Identifierhttp://hdl.handle.net/10722/265253
ISSN
2017 Impact Factor: 23.29
2015 SCImago Journal Rankings: 13.121
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYan, HHN-
dc.contributor.authorSiu, HC-
dc.contributor.authorLaw, SYK-
dc.contributor.authorHo, RSL-
dc.contributor.authorYue, SKS-
dc.contributor.authorTsui, WY-
dc.contributor.authorChan, D-
dc.contributor.authorChan, AS-
dc.contributor.authorMa, SKY-
dc.contributor.authorLam, KO-
dc.contributor.authorBartfeld, S-
dc.contributor.authorMan, HY-
dc.contributor.authorLee, CH-
dc.contributor.authorChan, ASY-
dc.contributor.authorWong, WHJ-
dc.contributor.authorCheng, SWP-
dc.contributor.authorChan, KW-
dc.contributor.authorZhang, J-
dc.contributor.authorShi, J-
dc.contributor.authorFan, X-
dc.contributor.authorKwong, DLW-
dc.contributor.authorMak, TW-
dc.contributor.authorYuen, ST-
dc.contributor.authorClevers, H-
dc.contributor.authorLeung, SY-
dc.date.accessioned2018-11-20T02:03:01Z-
dc.date.available2018-11-20T02:03:01Z-
dc.date.issued2018-
dc.identifier.citationCell Stem Cell, 2018, v. 23 n. 6, p. 882-897.e11-
dc.identifier.issn1934-5909-
dc.identifier.urihttp://hdl.handle.net/10722/265253-
dc.description.abstractGastric 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.-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at http://www.cellstemcell.com-
dc.relation.ispartofCell Stem Cell-
dc.subjectARHGAP fusions-
dc.subjectBiobank-
dc.subjectDrug screening-
dc.subjectEBV genome-
dc.subjectGastric cancer-
dc.subjectHeterogeneity-
dc.subjectOrganoid culture-
dc.subjectRHOA mutations-
dc.subjectTranscriptome sequencing-
dc.subjectWhole-exome sequencing-
dc.titleA Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening-
dc.typeArticle-
dc.identifier.emailYan, HHN: yanhelen@hkucc.hku.hk-
dc.identifier.emailSiu, HC: hcsiu@hku.hk-
dc.identifier.emailLaw, SYK: slaw@hku.hk-
dc.identifier.emailHo, RSL: hsl388@hku.hk-
dc.identifier.emailTsui, WY: wtsui112@hkucc.hku.hk-
dc.identifier.emailChan, D: dessyc@hku.hk-
dc.identifier.emailChan, AS: aschan@hku.hk-
dc.identifier.emailMa, SKY: stefma@hku.hk-
dc.identifier.emailLam, KO: lamkaon@hku.hk-
dc.identifier.emailMan, HY: alicemhy@HKUCC-COM.hku.hk-
dc.identifier.emailChan, ASY: asychan@hku.hk-
dc.identifier.emailWong, WHJ: jwhwong@hku.hk-
dc.identifier.emailCheng, SWP: swpc@HKUCC-COM.hku.hk-
dc.identifier.emailChan, KW: ankwchan@hkucc.hku.hk-
dc.identifier.emailZhang, J: jzhang1@hku.hk-
dc.identifier.emailKwong, DLW: dlwkwong@hku.hk-
dc.identifier.emailYuen, ST: styuen@hkucc.hku.hk-
dc.identifier.emailLeung, SY: suetyi@hku.hk-
dc.identifier.authorityYan, HHN=rp01994-
dc.identifier.authorityLaw, SYK=rp00437-
dc.identifier.authorityMa, SKY=rp00506-
dc.identifier.authorityLam, KO=rp01501-
dc.identifier.authorityWong, WHJ=rp02363-
dc.identifier.authorityZhang, J=rp01713-
dc.identifier.authorityKwong, DLW=rp00414-
dc.identifier.authorityLeung, SY=rp00359-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.stem.2018.09.016-
dc.identifier.pmid30344100-
dc.identifier.scopuseid_2-s2.0-85058484957-
dc.identifier.hkuros295956-
dc.identifier.volume23-
dc.identifier.issue6-
dc.identifier.spage882-
dc.identifier.epage897.e11-
dc.identifier.isiWOS:000452550400015-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats