1. Genomic and molecular characterization of esophageal squamous cell carcinoma
- Author
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Lin, De-Chen, Hao, Jia-Jie, Nagata, Yasunobu, Xu, Liang, Shang, Li, Meng, Xuan, Sato, Yusuke, Okuno, Yusuke, Varela, Ana Maria, Ding, Ling-Wen, Garg, Manoj, Liu, Li-Zhen, Yang, Henry, Yin, Dong, Shi, Zhi-Zhou, Jiang, Yan-Yi, Gu, Wen-Yue, Gong, Ting, Zhang, Yu, Xu, Xin, Kalid, Ori, Shacham, Sharon, Ogawa, Seishi, Wang, Ming-Rong, and Koeffler, H Phillip
- Subjects
Biological Sciences ,Genetics ,Human Genome ,Biotechnology ,Digestive Diseases ,Cancer ,Rare Diseases ,Animals ,Base Sequence ,Carcinoma ,Squamous Cell ,Cell Line ,Tumor ,DNA Copy Number Variations ,Esophageal Neoplasms ,Esophageal Squamous Cell Carcinoma ,Exome ,Genetic Vectors ,HEK293 Cells ,High-Throughput Nucleotide Sequencing ,Humans ,Image Processing ,Computer-Assisted ,Immunohistochemistry ,In Situ Hybridization ,Fluorescence ,Karyopherins ,Mice ,Mice ,SCID ,Microscopy ,Fluorescence ,Molecular Sequence Data ,Real-Time Polymerase Chain Reaction ,Receptors ,Cytoplasmic and Nuclear ,Reverse Transcriptase Polymerase Chain Reaction ,Sequence Analysis ,DNA ,Signal Transduction ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to those already known (TP53, PIK3CA and NOTCH1). Further SCNV evaluation, immunohistochemistry and biological analysis suggested their functional relevance in ESCC. Notably, RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently dysregulated by multiple molecular mechanisms in this cancer. Our approaches also uncovered many druggable candidates, and XPO1 was further explored as a therapeutic target because it showed both gene mutation and protein overexpression. Our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.
- Published
- 2014