Dulak AM, Stojanov P, Peng S, Lawrence MS, Fox C, Stewart C, Bandla S, Imamura Y, Schumacher SE, Shefler E, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45:478–86.
NOTES
Dulak, Austin MStojanov, PetarPeng, ShouyongLawrence, Michael SFox, CameronStewart, ChipBandla, SanthoshiImamura, YuSchumacher, Steven EShefler, EricaMcKenna, AaronCarter, Scott LCibulskis, KristianSivachenko, AndreySaksena, GordonVoet, DouglasRamos, Alex HAuclair, DanielThompson, KristinSougnez, CarrieOnofrio, Robert CGuiducci, CandaceBeroukhim, RameenZhou, ZhongrenLin, LinLin, JulesReddy, RishindraChang, AndrewLandrenau, RodneyPennathur, ArjunOgino, ShujiLuketich, James DGolub, Todd RGabriel, Stacey BLander, Eric SBeer, David GGodfrey, Tony EGetz, GadBass, Adam JengU54 HG003067/HG/NHGRI NIH HHS/P30 CA046592/CA/NCI NIH HHS/U54 CA163059/CA/NCI NIH HHS/R01 CA151993/CA/NCI NIH HHS/K08 CA134931/CA/NCI NIH HHS/CA130853/CA/NCI NIH HHS/CA46592/CA/NCI NIH HHS/CA090665/CA/NCI NIH HHS/Howard Hughes Medical Institute/P50 CA127003/CA/NCI NIH HHS/CA163059/CA/NCI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tNat Genet. 2013 May;45(5):478-86. doi: 10.1038/ng.2591. Epub 2013 Mar 24.
Abstract
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 potential activation of the RAC1 pathway as a contributor to EAC tumorigenesis.
Last updated on 02/17/2021