作者
Curtis R Pickering, Jiexin Zhang, Suk Young Yoo, Linnea Bengtsson, Shhyam Moorthy, David M Neskey, Mei Zhao, Marcus V Ortega Alves, Kyle Chang, Jennifer Drummond, Elsa Cortez, Tong-xin Xie, Di Zhang, Woonbok Chung, Jean-Pierre J Issa, Patrick A Zweidler-McKay, Xifeng Wu, Adel K El-Naggar, John N Weinstein, Jing Wang, Donna M Muzny, Richard A Gibbs, David A Wheeler, Jeffrey N Myers, Mitchell J Frederick
发表日期
2013/7/1
期刊
Cancer discovery
卷号
3
期号
7
页码范围
770-781
出版商
American Association for Cancer Research
简介
The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis of gene expression, copy number, methylation, and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, and TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of caspase-8 (CASP8) defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of …
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CR Pickering, J Zhang, SY Yoo, L Bengtsson… - Cancer discovery, 2013