Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms10380
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dc.titleMutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion
dc.contributor.authorYamamoto Y.
dc.contributor.authorWang X.
dc.contributor.authorBertrand D.
dc.contributor.authorKern F.
dc.contributor.authorZhang T.
dc.contributor.authorDuleba M.
dc.contributor.authorSrivastava S.
dc.contributor.authorKhor C.C.
dc.contributor.authorHu Y.
dc.contributor.authorWilson L.H.
dc.contributor.authorBlaszyk H.
dc.contributor.authorRolshud D.
dc.contributor.authorTeh M.
dc.contributor.authorLiu J.
dc.contributor.authorHowitt B.E.
dc.contributor.authorVincent M.
dc.contributor.authorCrum C.P.
dc.contributor.authorNagarajan N.
dc.contributor.authorHo K.Y.
dc.contributor.authorMcKeon F.
dc.contributor.authorXian W.
dc.date.accessioned2020-09-10T01:42:09Z
dc.date.available2020-09-10T01:42:09Z
dc.date.issued2016
dc.identifier.citationYamamoto 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
dc.identifier.issn20411723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175443
dc.description.abstractThe 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.
dc.publisherNature Publishing Group
dc.sourceUnpaywall 20200831
dc.subjectprotein p53
dc.subjectprotein tyrosine kinase
dc.subjectcells and cell components
dc.subjectenzyme activity
dc.subjectgene expression
dc.subjectgenomics
dc.subjectlesion
dc.subjectmutation
dc.subjectspectrum
dc.subjecttumor
dc.subjectadult
dc.subjectadult stem cell
dc.subjectArticle
dc.subjectBarrett esophagus
dc.subjectcancer growth
dc.subjectcancer patient
dc.subjectcancer risk
dc.subjectcancer stem cell
dc.subjectcell differentiation
dc.subjectcell isolation
dc.subjectcopy number variation
dc.subjectendoscopic biopsy
dc.subjectesophageal adenocarcinoma
dc.subjectgene amplification
dc.subjectgene frequency
dc.subjectgene mutation
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectimmunohistochemistry
dc.subjectin vitro study
dc.subjectmutational analysis
dc.subjectprecancer
dc.subjectproto oncogene
dc.subjectsingle nucleotide polymorphism
dc.subjectxenograft
dc.subjectanimal
dc.subjectBarrett esophagus
dc.subjectcell culture
dc.subjectgenetics
dc.subjectmale
dc.subjectmetabolism
dc.subjectmouse
dc.subjectmutation
dc.subjectpathology
dc.subjectprecancer
dc.subjectstem cell
dc.subjecttumor cell culture
dc.subjectAnimals
dc.subjectBarrett Esophagus
dc.subjectCell Differentiation
dc.subjectCells, Cultured
dc.subjectHumans
dc.subjectMale
dc.subjectMice
dc.subjectMutation
dc.subjectPrecancerous Conditions
dc.subjectStem Cells
dc.subjectTumor Cells, Cultured
dc.typeArticle
dc.contributor.departmentDEPT OF COMPUTER SCIENCE
dc.description.doi10.1038/ncomms10380
dc.description.sourcetitleNature Communications
dc.description.volume7
dc.description.page10380
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