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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Modelling hereditary diffuse gastric cancer initiation using transgenic mouse-derived gastric organoids and single-cell sequencing
Journal of Pathology, Volume 254, No. 3, Year 2021
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Description
Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome caused by germline variants in CDH1, the gene encoding the cell–cell adhesion molecule E-cadherin. Loss of E-cadherin in cancer is associated with cellular dedifferentiation and poor prognosis, but the mechanisms through which CDH1 loss initiates HDGC are not known. Using single-cell RNA sequencing, we explored the transcriptional landscape of a murine organoid model of HDGC to characterize the impact of CDH1 loss in early tumourigenesis. Progenitor populations of stratified squamous and simple columnar epithelium, characteristic of the mouse stomach, showed lineage-specific transcriptional programs. Cdh1 inactivation resulted in shifts along the squamous differentiation trajectory associated with aberrant expression of genes central to gastrointestinal epithelial differentiation. Cytokeratin 7 (CK7), encoded by the differentiation-dependent gene Krt7, was a specific marker for early neoplastic lesions in CDH1 carriers. Our findings suggest that deregulation of developmental transcriptional programs may precede malignancy in HDGC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors & Co-Authors
Dixon, Katherine
Canada, Vancouver
The University of British Columbia
Brew, Tom
New Zealand, Dunedin
University of Otago
Farnell, David
Canada, Vancouver
University of British Columbia, Faculty of Medicine
Godwin, Tanis D.
New Zealand, Dunedin
University of Otago
Cheung, Simon
Canada, Vancouver
Vancouver Coastal Health
Chow, Christine
Canada, Vancouver
The University of British Columbia
Ta, Monica
Canada, Vancouver
The University of British Columbia
Ho, Germain
Canada, Vancouver
British Columbia Cancer Agency
Bui, Minh
Canada, Vancouver
British Columbia Cancer Agency
Douglas, J. Maxwell
Canada, Vancouver
British Columbia Cancer Agency
Campbell, Kieran R.
Canada, Vancouver
British Columbia Cancer Agency
El-Naggar, Amal M.
Canada, Vancouver
British Columbia Cancer Agency
Egypt, Shibin el Kom
Menoufia University Faculty of Medicine
Kaurah, Pardeep
Canada, Vancouver
British Columbia Cancer Agency
Kalloger, Steve E.
Canada, Vancouver
University of British Columbia, Faculty of Medicine
Lim, Howard J.
Canada, Vancouver
British Columbia Cancer Agency
Schaeffer, David F.
Canada, Vancouver
University of British Columbia, Faculty of Medicine
Canada, Vancouver
Vancouver Coastal Health
Cochrane, Dawn
Canada, Vancouver
British Columbia Cancer Agency
Guilford, Parry
New Zealand, Dunedin
University of Otago
Huntsman, David G.
Canada, Vancouver
University of British Columbia, Faculty of Medicine
Statistics
Citations: 19
Authors: 19
Affiliations: 6
Identifiers
Doi:
10.1002/path.5675
ISSN:
00223417
e-ISSN:
10969896
Research Areas
Cancer
Genetics And Genomics