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Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma
Barrett’s esophagus, is thought to progress to esophageal adenocarcinoma (EAC) through a step-wise 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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552571/ https://www.ncbi.nlm.nih.gov/pubmed/26192918 http://dx.doi.org/10.1038/ng.3343 |
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author | 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 Stewart, Chip Stojanov, Petar Seepo, Sara Lawrence, Michael S. Ferrer-Torres, Daysha Lin, Jules Chang, Andrew C. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Getz, Gad Carter, Scott L. Bass, Adam J. |
author_facet | 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 Stewart, Chip Stojanov, Petar Seepo, Sara Lawrence, Michael S. Ferrer-Torres, Daysha Lin, Jules Chang, Andrew C. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Getz, Gad Carter, Scott L. Bass, Adam J. |
author_sort | Stachler, Matthew D. |
collection | PubMed |
description | Barrett’s esophagus, is thought to progress to esophageal adenocarcinoma (EAC) through a step-wise 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. |
format | Online Article Text |
id | pubmed-4552571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-45525712016-03-01 Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma 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 Stewart, Chip Stojanov, Petar Seepo, Sara Lawrence, Michael S. Ferrer-Torres, Daysha Lin, Jules Chang, Andrew C. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Getz, Gad Carter, Scott L. Bass, Adam J. Nat Genet Article Barrett’s esophagus, is thought to progress to esophageal adenocarcinoma (EAC) through a step-wise 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. 2015-07-20 2015-09 /pmc/articles/PMC4552571/ /pubmed/26192918 http://dx.doi.org/10.1038/ng.3343 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article 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 Stewart, Chip Stojanov, Petar Seepo, Sara Lawrence, Michael S. Ferrer-Torres, Daysha Lin, Jules Chang, Andrew C. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Getz, Gad Carter, Scott L. Bass, Adam J. Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma |
title | Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma |
title_full | Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma |
title_fullStr | Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma |
title_full_unstemmed | Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma |
title_short | Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma |
title_sort | paired exome analysis of barrett’s esophagus and adenocarcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552571/ https://www.ncbi.nlm.nih.gov/pubmed/26192918 http://dx.doi.org/10.1038/ng.3343 |
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