Paired exome analysis of Barrett's esophagus and adenocarcinoma
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 e...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/1721.1/105360 |
| _version_ | 1826197858301247488 |
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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 Beer, David G Getz, Gad Carter, Scott L Bass, Adam J Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 Beer, David G Getz, Gad Carter, Scott L Bass, Adam J Lander, Eric Steven |
| author_sort | Stachler, Matthew D |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:54:54Z |
| format | Article |
| id | mit-1721.1/105360 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:54:54Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1053602022-09-30T23:53:38Z 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 Beer, David G Getz, Gad Carter, Scott L Bass, Adam J Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven 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. National Institutes of Health (U.S.) (Grant T32 HL007627) National Human Genome Research Institute (U.S.) Large-Scale Sequencing Program (Grant U54 HG0003067) 2016-11-18T15:56:08Z 2016-11-18T15:56:08Z 2015-07 2015-02 Article http://purl.org/eprint/type/JournalArticle 1061-4036 1546-1718 http://hdl.handle.net/1721.1/105360 Stachler, Matthew D et al. “Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma.” Nature Genetics 47.9 (2015): 1047–1055. en_US http://dx.doi.org/10.1038/ng.3343 Nature Genetics 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. application/pdf Nature Publishing Group PMC |
| spellingShingle | 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 Beer, David G Getz, Gad Carter, Scott L Bass, Adam J Lander, Eric Steven 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 |
| url | http://hdl.handle.net/1721.1/105360 |
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