Genomic and molecular characterization of esophageal squamous cell carcinoma.
De-Chen LinJia-Jie HaoYasunobu NagataLiang XuLi ShangXuan MengYusuke SatoYusuke OkunoAna Maria VarelaLing-Wen DingManoj GargLi-Zhen LiuHenry YangDong YinZhi-Zhou ShiYan-Yi JiangWen-Yue GuTing GongYu ZhangXin XuOri KalidSharon ShachamSeishi OgawaMing-Rong WangH Phillip KoefflerPublished in: Nature genetics (2014)
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.
Keyphrases
- copy number
- cell cycle
- genome wide
- mitochondrial dna
- cell proliferation
- adipose tissue
- dna methylation
- papillary thyroid
- signaling pathway
- pi k akt
- oxidative stress
- fatty acid
- squamous cell carcinoma
- squamous cell
- transcription factor
- small molecule
- binding protein
- young adults
- protein kinase
- lymph node metastasis
- clinical evaluation