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

被引：598

作者：

Dulak, Austin M. ^{[1
,2
,3
]}

Stojanov, Petar ^{[1
,2
,3
]}

Peng, Shouyong ^{[1
,2
]}

Lawrence, Michael S. ^{[2
]}

Fox, Cameron ^{[1
]}

Stewart, Chip ^{[2
]}

Bandla, Santhoshi ^{[4
]}

Imamura, Yu ^{[1
]}

Schumacher, Steven E. ^{[1
,2
]}

Shefler, Erica ^{[2
]}

McKenna, Aaron ^{[2
]}

Carter, Scott L. ^{[2
]}

Cibulskis, Kristian ^{[2
]}

Sivachenko, Andrey ^{[2
]}

Saksena, Gordon ^{[2
]}

Voet, Douglas ^{[2
]}

Ramos, Alex H. ^{[2
]}

Auclair, Daniel ^{[2
]}

Thompson, Kristin ^{[2
]}

Sougnez, Carrie ^{[2
]}

Onofrio, Robert C. ^{[2
]}

Guiducci, Candace ^{[2
]}

Beroukhim, Rameen ^{[1
,2
,5
,6
]}

Zhou, Zhongren ^{[4
]}

Lin, Lin ^{[7
]}

Lin, Jules ^{[7
]}

Reddy, Rishindra ^{[7
]}

Chang, Andrew ^{[7
]}

Landrenau, Rodney ^{[8
]}

Pennathur, Arjun ^{[8
]}

Ogino, Shuji ^{[1
,6
,9
,10
]}

Luketich, James D. ^{[8
]}

Golub, Todd R. ^{[1
,2
,6
,11
]}

Gabriel, Stacey B. ^{[2
]}

Lander, Eric S. ^{[2
,3
,6
]}

Beer, David G. ^{[7
]}

Godfrey, Tony E. ^{[4
]}

Getz, Gad ^{[2
,12
,13
]}

Bass, Adam J. ^{[1
,2
,5
,6
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA

[3] MIT, Dept Biol, Cambridge, MA USA

[4] Univ Rochester, Dept Surg, Rochester, NY USA

[5] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[7] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA

[8] Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA

[9] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[10] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[11] Howard Hughes Med Inst, Chevy Chase, MD USA

[12] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[13] Dept Pathol, Boston, MA USA

来源：

NATURE GENETICS | 2013年 / 45卷 / 05期

基金：

美国国家卫生研究院;

关键词：

ERBB2 KINASE DOMAIN; SOMATIC MUTATIONS; GENE-MUTATIONS; BARRETT-ESOPHAGUS; STRUCTURAL BASIS; TROYER-SYNDROME; RAC ACTIVATION; CELL-ADHESION; LUNG-CANCER; EXPRESSION;

D O I：

10.1038/ng.2591

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a 5-year survival rate of similar to 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.

引用

页码：478 / U37

页数：11

共 50 条

[41] Whole exome sequencing identifies lncRNA GAS8-AS1 and LPAR4 as novel papillary thyroid carcinoma driver alternations [J].

Pan, Wenting ;

Zhou, Liqing ;

Ge, Minghua ;

Zhang, Bin ;

Yang, Xinyu ;

Xiong, Xiangyu ;

Fu, Guobin ;

Zhang, Jian ;

Nie, Xilin ;

Li, Hongmin ;

Tang, Xiaohu ;

Wei, Jinyu ;

Shao, Mingming ;

Zheng, Jian ;

Yuan, Qipeng ;

Tan, Wen ;

Wu, Chen ;

Yang, Ming ;

Lin, Dongxin .

HUMAN MOLECULAR GENETICS, 2016, 25 (09) :1875-1884

[42] Whole-genome Sequencing of Follicular Thyroid Carcinomas Reveal Recurrent Mutations in MicroRNA Processing Subunit DGCR8 [J].

Paulsson, Johan O. ;

Rafati, Nima ;

DiLorenzo, Sebastian ;

Chen, Yi ;

Haglund, Felix ;

Zedenius, Jan ;

Juhlin, C. Christofer .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2021, 106 (11) :3265-3282

[43] Integration of whole-genome sequencing and functional screening identifies a prognostic signature for lung metastasis in triple-negative breast cancer [J].

Xie, Guangdong ;

Yang, Haiyuan ;

Ma, Ding ;

Sun, Yihua ;

Chen, Haiquan ;

Hu, Xin ;

Jiang, Yi-Zhou ;

Shao, Zhi-Ming .

INTERNATIONAL JOURNAL OF CANCER, 2019, 145 (10) :2850-2860

[44] Whole-Genome Sequencing of Retinoblastoma Reveals the Diversity of Rearrangements Disrupting RB1 and Uncovers a Treatment-Related Mutational Signature [J].

Davies, Helen R. ;

Broad, Kevin D. ;

Onadim, Zerrin ;

Price, Elizabeth A. ;

Zou, Xueqing ;

Sheriff, Ibrahim ;

Karaa, Esin Kotiloglu ;

Scheimberg, Irene ;

Reddy, M. Ashwin ;

Sagoo, Mandeep S. ;

Ohnuma, Shin-ichi ;

Nik-Zainal, Serena .

CANCERS, 2021, 13 (04) :1-19

[45] Whole-Genome Sequencing Identifies PPARGC1A as a Putative Modifier of Cancer Risk in BRCA1/2 Mutation Carriers [J].

Zhu, Qianqian ;

Wang, Jie ;

Yu, Han ;

Hu, Qiang ;

Bateman, Nicholas W. ;

Long, Mark ;

Rosario, Spencer ;

Schultz, Emily ;

Dalgard, Clifton L. ;

Wilkerson, Matthew D. ;

Sukumar, Gauthaman ;

Huang, Ruea-Yea ;

Kaur, Jasmine ;

Lele, Shashikant B. ;

Zsiros, Emese ;

Villella, Jeannine ;

Lugade, Amit ;

Moysich, Kirsten ;

Conrads, Thomas P. ;

Maxwell, George L. ;

Odunsi, Kunle .

CANCERS, 2022, 14 (10)

[46] Whole-exome sequencing analysis identifies distinct mutational profile and novel prognostic biomarkers in primary gastrointestinal diffuse large B-cell lymphoma [J].

Li, Shan-Shan ;

Zhai, Xiao-Hui ;

Liu, Hai-Ling ;

Liu, Ting-Zhi ;

Cao, Tai-Yuan ;

Chen, Dong-Mei ;

Xiao, Le-Xin ;

Gan, Xiao-Qin ;

Cheng, Ke ;

Hong, Wan-Jia ;

Huang, Yan ;

Lian, Yi-Fan ;

Xiao, Jian .

EXPERIMENTAL HEMATOLOGY & ONCOLOGY, 2022, 11 (01)

[47] Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides [J].

Egan, Jan B. ;

Shi, Chang-Xin ;

Tembe, Waibhav ;

Christoforides, Alexis ;

Kurdoglu, Ahmet ;

Sinari, Shripad ;

Middha, Sumit ;

Asmann, Yan ;

Schmidt, Jessica ;

Braggio, Esteban ;

Keats, Jonathan J. ;

Fonseca, Rafael ;

Bergsagel, P. Leif ;

Craig, David W. ;

Carpten, John D. ;

Stewart, A. Keith .

BLOOD, 2012, 120 (05) :1060-1066

[48] Whole-genome sequencing identifies ADGRG6 enhancer mutations and FRS2 duplications as angiogenesis-related drivers in bladder cancer [J].

Wu, Song ;

Ou, Tong ;

Xing, Nianzeng ;

Lu, Jiang ;

Wan, Shengqing ;

Wang, Changxi ;

Zhang, Xi ;

Yang, Feiya ;

Huang, Yi ;

Cai, Zhiming .

NATURE COMMUNICATIONS, 2019, 10 (1)

[49] Next-Generation Sequencing Whole-Genome Analysis for Targeted Treatment Approach of Metastatic Bartholin Gland Adenocarcinoma: An Emblematic Case Report and Review of the Literature [J].

Maccio, Antonio ;

Donisi, Clelia ;

Sanna, Elisabetta ;

Chiappe, Giacomo ;

Nemolato, Sonia ;

Melis, Luca ;

Oppi, Sara ;

Mola, Brunella ;

Madeddu, Clelia .

DIAGNOSTICS, 2021, 11 (11)

[50] Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry [J].

Protasova, Maria S. ;

Grigorenko, Anastasia P. ;

Tyazhelova, Tatiana V. ;

Andreeva, Tatiana V. ;

Reshetov, Denis A. ;

Gusev, Fedor E. ;

Laptenko, Alexander E. ;

Kuznetsova, Irina L. ;

Goltsov, Andrey Y. ;

Klyushnikov, Sergey A. ;

Illarioshkin, Sergey N. ;

Rogaev, Evgeny I. .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2016, 24 (04) :550-555

← 1 2 3 4 5 →