Genetic landscape of esophageal squamous cell carcinoma

被引：587

作者：

Gao, Yi-Bo ^{[1
]}

Chen, Zhao-Li ^{[1
]}

Li, Jia-Gen ^{[1
]}

Hu, Xue-Da ^{[1
]}

Shi, Xue-Jiao ^{[1
]}

Sun, Zeng-Miao ^{[1
]}

Zhang, Fan ^{[1
]}

Zhao, Zi-Ran ^{[2
,3
]}

Li, Zi-Tong ^{[2
,3
]}

Liu, Zi-Yuan ^{[1
]}

Zhao, Yu-Da ^{[1
]}

Sun, Jian ^{[1
]}

Zhou, Cheng-Cheng ^{[1
]}

Yao, Ran ^{[1
]}

Wang, Su-Ya ^{[1
]}

Wang, Pan ^{[2
,3
]}

Sun, Nan ^{[1
]}

Zhang, Bai-Hua ^{[1
]}

Dong, Jing-Si ^{[1
]}

Yu, Yue ^{[1
]}

Luo, Mei ^{[1
]}

Feng, Xiao-Li ^{[4
]}

Shi, Su-Sheng ^{[4
]}

Zhou, Fang ^{[1
]}

Tan, Feng-Wei ^{[1
]}

Qiu, Bin ^{[1
]}

Li, Ning ^{[1
]}

Shao, Kang ^{[1
]}

Zhang, Li-Jian ^{[5
]}

Zhang, Lan-Jun ^{[6
]}

Xue, Qi ^{[1
]}

Gao, Shu-Geng ^{[1
]}

He, Jie ^{[1
]}

机构：

[1] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Thorac Surg, Beijing 100730, Peoples R China

[2] Peking Union Med Coll, Dept Clin Med, Beijing 100021, Peoples R China

[3] Chinese Acad Med Sci, Beijing 100730, Peoples R China

[4] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Pathol, Beijing 100730, Peoples R China

[5] Peking Univ, Canc Hosp, Dept Thorac Surg, Beijing 100871, Peoples R China

[6] Sun Yat Sen Univ, Ctr Canc, Dept Thorac Surg, Guangzhou 510275, Guangdong, Peoples R China

来源：

NATURE GENETICS | 2014年 / 46卷 / 10期

基金：

中国国家自然科学基金;

关键词：

GENOME-WIDE ASSOCIATION; RECURRENT SOMATIC MUTATIONS; SUSCEPTIBILITY LOCI; CANCER GENOME; LUNG-CANCER; GASTRIC ADENOCARCINOMA; FREQUENT MUTATION; LIM PROTEIN; EXOME; FAMILY;

D O I：

10.1038/ng.3076

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers'. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (1UB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

引用

页码：1097 / 1102

页数：6

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