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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 |
Appears in Collections: | Staff Publications Elements |
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