Paired exome analysis of Barrett's esophagus and adenocarcinoma
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Lander_Paired genomic.pdf
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2.12 MB
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Author(s)
Stachler, Matthew D
Taylor-Weiner, Amaro
Peng, Shouyong
McKenna, Aaron
Agoston, Agoston T
Odze, Robert D
Davison, Jon M
Nason, Katie S
Loda, Massimo
Leshchiner, Ignaty
Date Issued
July 2015
Journal
Nature Genetics
Publisher
Nature Publishing Group
Citation
Stachler, Matthew D et al. “Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma.” Nature Genetics 47.9 (2015): 1047–1055.
Version
Author's final manuscript
Abstract
Barrett’s esophagus, is thought to progress to esophageal adenocarcinoma (EAC) through a stepwise progression with loss of CDKN2A followed by p53 inactivation and aneuploidy. Here, we present whole exome sequencing from 25 pairs of EAC and Barrett’s and five patients whose Barrett’s and tumor were extensively sampled. Our analysis revealed that oncogene amplification typically occurred as a late event and that TP53 mutations often occur early in Barrett’s progression, including in non-dysplastic epithelium. Reanalysis of additional EAC exome data
revealed that the majority (62.5%) of EACs emerged following genome doubling and that tumors with genomic doubling had different patterns of genomic alterations with more frequent oncogenic amplifications and less frequent inactivation of tumor suppressors, including CDKN2A. These data
suggest that many EACs emerge not through gradual accumulation of tumor suppressor alterations but rather through a more direct path whereby a TP53-mutant cell undergoes genome doubling, followed by acquisition of oncogenic amplifications.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/ng.3343
