Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity

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Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity

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Title: Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity
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.

Note: Order does not necessarily reflect citation order of authors.

Citation: Dulak, A. M., P. Stojanov, S. Peng, M. S. Lawrence, C. Fox, C. Stewart, S. Bandla, et al. 2013. “Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.” Nature genetics 45 (5): 10.1038/ng.2591. doi:10.1038/ng.2591. http://dx.doi.org/10.1038/ng.2591.
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Abstract: 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.
Published Version: doi:10.1038/ng.2591
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678719/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879006
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