Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms10380
Title: Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion
Authors: Yamamoto Y.
Wang X.
Bertrand D.
Kern F.
Zhang T.
Duleba M.
Srivastava S.
Khor C.C.
Hu Y.
Wilson L.H.
Blaszyk H.
Rolshud D.
Teh M.
Liu J.
Howitt B.E.
Vincent M.
Crum C.P.
Nagarajan N. 
Ho K.Y.
McKeon F.
Xian W.
Keywords: protein p53
protein tyrosine kinase
cells and cell components
enzyme activity
gene expression
genomics
lesion
mutation
spectrum
tumor
adult
adult stem cell
Article
Barrett esophagus
cancer growth
cancer patient
cancer risk
cancer stem cell
cell differentiation
cell isolation
copy number variation
endoscopic biopsy
esophageal adenocarcinoma
gene amplification
gene frequency
gene mutation
human
human cell
human tissue
immunohistochemistry
in vitro study
mutational analysis
precancer
proto oncogene
single nucleotide polymorphism
xenograft
animal
Barrett esophagus
cell culture
genetics
male
metabolism
mouse
mutation
pathology
precancer
stem cell
tumor cell culture
Animals
Barrett Esophagus
Cell Differentiation
Cells, Cultured
Humans
Male
Mice
Mutation
Precancerous Conditions
Stem Cells
Tumor Cells, Cultured
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Yamamoto Y., Wang X., Bertrand D., Kern F., Zhang T., Duleba M., Srivastava S., Khor C.C., Hu Y., Wilson L.H., Blaszyk H., Rolshud D., Teh M., Liu J., Howitt B.E., Vincent M., Crum C.P., Nagarajan N., Ho K.Y., McKeon F., Xian W. (2016). Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion. Nature Communications 7 : 10380. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms10380
Abstract: The precancerous lesion known as Barrett's oesophagus can evolve to oesophageal adenocarcinoma in decades-long processes of regenerative growth. Here we report the isolation and propagation of distinct, patient-matched stem cells of Barrett's, gastric and oesophageal epithelia that yield divergent tumour types following in vitro transformation and xenografting. Genomic analyses reveal a broad mutational spectrum unique to Barrett's stem cells that likely reflects their risk for oncogenesis. Remarkably, 25% of cases show no cancer-related genomic changes, suggesting that Barrett's initiates without driver mutations. Most cases, however, sustain patterns of deletions almost identical to adenocarcinoma though tumour-associated gene amplifications were absent. Notably, those suspected of low-grade dysplasia have p53 mutations or undergo amplifications of proto-oncogenes and receptor tyrosine kinases, implicating these events in lethal transitions. Our findings suggest paths for the initiation and progression of Barrett's and define a discrete stem cell underlying its regenerative growth whose eradication could prevent oesophageal adenocarcinoma.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/175443
ISSN: 20411723
DOI: 10.1038/ncomms10380
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