Clinical Research Papers:
Somatic copy number alterations detected by ultra-deep targeted sequencing predict prognosis in oral cavity squamous cell carcinoma
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Chien-Hua Peng1,*, Chun-Ta Liao2,3,*, Ka-Pou Ng4, An-Shun Tai4, Shih-Chi Peng5, Jen-Pao Yeh4, Shu-Jen Chen6, Kuo-Chien Tsao7,8, Tzu-Chen Yen5 and Wen-Ping Hsieh2
1 Departments of Resource Center for Clinical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
2 Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
3 Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
4 Institute of Statistics, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
5 Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
6 Department of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.
7 Medical Biotechnology and Laboratory Science, Research Center for Emerging Viral Infections, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
8 Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
* These two authors have contributed equally to this work
Tzu-Chen Yen, email:
Wen-Ping Hsieh, email:
Keywords: ultradeep-targeted sequencing, oral cavity squamous cell carcinoma, copy number alteration, biomarker, clinically actionable genes
Received: February 11, 2015 Accepted: May 23, 2015 Published: June 02, 2015
Background: Ultra-deep targeted sequencing (UDT-Seq) has advanced our knowledge on the incidence and functional significance of somatic mutations. However, the utility of UDT-Seq in detecting copy number alterations (CNAs) remains unclear. With the goal of improving molecular prognostication and identifying new therapeutic targets, we designed this study to assess whether UDT-Seq may be useful for detecting CNA in oral cavity squamous cell carcinoma (OSCC).
Methods: We sequenced a panel of clinically actionable cancer mutations in 310 formalin-fixed paraffin-embedded OSCC specimens. A linear model was developed to overcome uneven coverage across target regions and multiple samples. The 5-year rates of secondary primary tumors, local recurrence, neck recurrence, distant metastases, and survival served as the outcome measures. We confirmed the prognostic significance of the CNA signatures in an independent sample of 105 primary OSCC specimens.
Results: The CNA burden across 10 targeted genes was found to predict prognosis in two independent cohorts. FGFR1 and PIK3CAamplifications were associated with prognosis independent of clinical risk factors. Genes exhibiting CNA were clustered in the proteoglycan metabolism, the FOXO signaling, and the PI3K-AKT signaling pathways, for which targeted drugs are already available or currently under development.
Conclusions: UDT-Seq is clinically useful to identify CNA, which significantly improve the prognostic information provided by traditional clinicopathological risk factors in OSCC patients.
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