Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.
Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.
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DOI：
10.1038/ng.2591
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发表时间：
2013-05
期刊：
影响因子：
30.8
通讯作者：
Bass, Adam J.
中科院分区：
文献类型：
--
作者：
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;Carter, Scott L.;Cibulskis, Kristian;Sivachenko, Andrey;Saksena, Gordon;Voet, Douglas;Ramos, Alex H.;Auclair, Daniel;Thompson, Kristin;Sougnez, Carrie;Onofrio, Robert C.;Guiducci, Candace;Beroukhim, Rameen;Zhou, Zhongren;Lin, Lin;Lin, Jules;Reddy, Rishindra;Chang, Andrew;Landrenau, Rodney;Pennathur, Arjun;Ogino, Shuji;Luketich, James D.;Golub, Todd R.;Gabriel, Stacey B.;Lander, Eric S.;Beer, David G.;Godfrey, Tony E.;Getz, Gad;Bass, Adam J.
食管腺癌(EAC)的发病率在过去30年中上升了600%。由于EAC的五年生存率为15%，寻找新的治疗靶点是非常重要的。我们分析了149对EAC肿瘤/正常对的全外显子组测序的突变谱，其中15对也进行了全基因组测序。我们发现了一种突变特征，这种突变特征是由AA二核苷酸A到C转换的高流行率定义的。对外显子组数据的统计分析发现有26个基因发生了显著突变。在这些基因中，有四个(TP53、CDKN2A、Smad4和PIK3CA)以前被认为与EAC有关。新的显著突变基因包括染色质修饰因子和候选贡献者：SPG20、TLR4、ELMO1和DOCK2。对EAC衍生的ELMO1突变的功能分析显示，细胞侵袭增加。因此，我们提出了一个新的假设，即RAC1通路的潜在激活可能是EAC肿瘤发生的一个贡献者。
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.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.3
作者：
Eden E;Lipson D;Yogev S;Yakhini Z
通讯作者：
Yakhini Z
影响因子：
5.6
作者：
Farris, Alton B., III;Demicco, Elizabeth G.;Mino-Kenudson, Mari
通讯作者：
Mino-Kenudson, Mari
DOI：
10.1093/jnci/dji403
发表时间：
2005-12-07
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Bauer, AK;Dixon, D;Kleeberger, SR
通讯作者：
Kleeberger, SR
影响因子：
64.8
作者：
Berger, Michael F.;Hodis, Eran;Heffernan, Timothy P.;Deribe, Yonathan Lissanu;Lawrence, Michael S.;Protopopov, Alexei;Ivanova, Elena;Watson, Ian R.;Nickerson, Elizabeth;Ghosh, Papia;Zhang, Hailei;Zeid, Rhamy;Ren, Xiaojia;Cibulskis, Kristian;Sivachenko, Andrey Y.;Wagle, Nikhil;Sucker, Antje;Sougnez, Carrie;Onofrio, Robert;Ambrogio, Lauren;Auclair, Daniel;Fennell, Timothy;Carter, Scott L.;Drier, Yotam;Stojanov, Petar;Singer, Meredith A.;Voet, Douglas;Jing, Rui;Saksena, Gordon;Barretina, Jordi;Ramos, Alex H.;Pugh, Trevor J.;Stransky, Nicolas;Parkin, Melissa;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Wargo, Jennifer;Schadendorf, Dirk;Meyerson, Matthew;Gabriel, Stacey B.;Golub, Todd R.;Wagner, Stephan N.;Lander, Eric S.;Getz, Gad;Chin, Lynda;Garraway, Levi A.
通讯作者：
Garraway, Levi A.