作者
Austin M Dulak, Petar Stojanov, Shouyong Peng, Michael S Lawrence, Cameron Fox, Chip Stewart, Santhoshi Bandla, Yu Imamura, Steven E Schumacher, Erica Shefler, Aaron McKenna, Scott L Carter, Kristian Cibulskis, Andrey Sivachenko, Gordon Saksena, Douglas Voet, Alex H Ramos, Daniel Auclair, Kristin Thompson, Carrie Sougnez, Robert C Onofrio, Candace Guiducci, Rameen Beroukhim, Zhongren Zhou, Lin Lin, Jules Lin, Rishindra Reddy, Andrew Chang, Rodney Landrenau, Arjun Pennathur, Shuji Ogino, James D Luketich, Todd R Golub, Stacey B Gabriel, Eric S Lander, David G Beer, Tony E Godfrey, Gad Getz, Adam J Bass
发表日期
2013/5
期刊
Nature genetics
卷号
45
期号
5
页码范围
478-486
出版商
Nature Publishing Group US
简介
The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a 5-year survival rate of ∼15%, the identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole-exome sequencing of 149 EAC tumor-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>C transversions at AA dinucleotides. Statistical analysis of exome data identified 26 significantly mutated genes. Of these genes, five (TP53, CDKN2A, SMAD4, ARID1A and PIK3CA) have previously been implicated in EAC. The new significantly mutated genes include chromatin-modifying factors and candidate contributors SPG20, TLR4, ELMO1 and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 identifies increased cellular invasion. Therefore, we suggest the …
学术搜索中的文章
AM Dulak, P Stojanov, S Peng, MS Lawrence, C Fox… - Nature genetics, 2013