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Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity
The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/normal pairs, 15 of whi...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2013
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678719/ https://www.ncbi.nlm.nih.gov/pubmed/23525077 http://dx.doi.org/10.1038/ng.2591 |
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| author | Dulak, Austin M. Stojanov, Petar Peng, Shouyong Lawrence, Michael S. Fox, Cameron Stewart, Chip Bandla, Santhoshi Imamura, Yu Schumacher, Steven E. Shefler, Erica McKenna, Aaron Cibulskis, Kristian Sivachenko, Andrey Carter, Scott L. Saksena, Gordon Voet, Douglas Ramos, Alex H. Auclair, Daniel Thompson, Kristin Sougnez, Carrie Onofrio, Robert C. Guiducci, Candace Beroukhim, Rameen Zhou, David Lin, Lin Lin, Jules Reddy, Rishindra Chang, Andrew Luketich, James D. Pennathur, Arjun Ogino, Shuji Golub, Todd R. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Godfrey, Tony E. Getz, Gad Bass, Adam J. |
| author_facet | Dulak, Austin M. Stojanov, Petar Peng, Shouyong Lawrence, Michael S. Fox, Cameron Stewart, Chip Bandla, Santhoshi Imamura, Yu Schumacher, Steven E. Shefler, Erica McKenna, Aaron Cibulskis, Kristian Sivachenko, Andrey Carter, Scott L. Saksena, Gordon Voet, Douglas Ramos, Alex H. Auclair, Daniel Thompson, Kristin Sougnez, Carrie Onofrio, Robert C. Guiducci, Candace Beroukhim, Rameen Zhou, David Lin, Lin Lin, Jules Reddy, Rishindra Chang, Andrew Luketich, James D. Pennathur, Arjun Ogino, Shuji Golub, Todd R. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Godfrey, Tony E. Getz, Gad Bass, Adam J. |
| author_sort | Dulak, Austin M. |
| collection | PubMed |
| description | The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a mutational signature defined by a high prevalence of A to C transversions at AA dinucleotides. Statistical analysis of exome data identified significantly mutated 26 genes. Of these genes, four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include chromatin modifying factors and candidate contributors: SPG20, TLR4, ELMO1, and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 reveal increased cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis. |
| format | Online Article Text |
| id | pubmed-3678719 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2013 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-36787192013-11-01 Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity Dulak, Austin M. Stojanov, Petar Peng, Shouyong Lawrence, Michael S. Fox, Cameron Stewart, Chip Bandla, Santhoshi Imamura, Yu Schumacher, Steven E. Shefler, Erica McKenna, Aaron Cibulskis, Kristian Sivachenko, Andrey Carter, Scott L. Saksena, Gordon Voet, Douglas Ramos, Alex H. Auclair, Daniel Thompson, Kristin Sougnez, Carrie Onofrio, Robert C. Guiducci, Candace Beroukhim, Rameen Zhou, David Lin, Lin Lin, Jules Reddy, Rishindra Chang, Andrew Luketich, James D. Pennathur, Arjun Ogino, Shuji Golub, Todd R. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Godfrey, Tony E. Getz, Gad Bass, Adam J. Nat Genet Article The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a mutational signature defined by a high prevalence of A to C transversions at AA dinucleotides. Statistical analysis of exome data identified significantly mutated 26 genes. Of these genes, four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include chromatin modifying factors and candidate contributors: SPG20, TLR4, ELMO1, and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 reveal increased cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis. 2013-03-24 2013-05 /pmc/articles/PMC3678719/ /pubmed/23525077 http://dx.doi.org/10.1038/ng.2591 Text en Users may view, print, copy, download and 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 Dulak, Austin M. Stojanov, Petar Peng, Shouyong Lawrence, Michael S. Fox, Cameron Stewart, Chip Bandla, Santhoshi Imamura, Yu Schumacher, Steven E. Shefler, Erica McKenna, Aaron Cibulskis, Kristian Sivachenko, Andrey Carter, Scott L. Saksena, Gordon Voet, Douglas Ramos, Alex H. Auclair, Daniel Thompson, Kristin Sougnez, Carrie Onofrio, Robert C. Guiducci, Candace Beroukhim, Rameen Zhou, David Lin, Lin Lin, Jules Reddy, Rishindra Chang, Andrew Luketich, James D. Pennathur, Arjun Ogino, Shuji Golub, Todd R. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Godfrey, Tony E. Getz, Gad Bass, Adam J. Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity |
| title | Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity |
| title_full | Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity |
| title_fullStr | Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity |
| title_full_unstemmed | Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity |
| title_short | Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity |
| title_sort | exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678719/ https://www.ncbi.nlm.nih.gov/pubmed/23525077 http://dx.doi.org/10.1038/ng.2591 |
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