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Oncotarget. 2017 Jul 28;8(49):85326-85340. doi: 10.18632/oncotarget.19674. eCollection 2017 Oct 17.

Whole-exome sequencing reveals novel mutations and epigenetic regulation in hypopharyngeal carcinoma.

Wu P1, Wu H2,3,4, Tang Y1, Luo S1, Fang X1, Xie C1, He J1, Zhao S1, Wang X2,3, Xu J2,3, Chen X2,3, Li D2,3, Yang H5,6, Wang J5,6.

Author information

Department of Otorhinolaryngology Head & Neck Surgery, Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha 410008, China.
Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.
BGI-Shenzhen, Shenzhen 518083, China.
James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.


Hypopharyngeal cancer (HPC) frequently presents at an advanced stage, resulting in poor prognosis. Although combined surgical therapy and chemoradiotherapy have improved the survival for patients with HPC over the past 3 decades, the mortality rate in late-stage diagnosis of HPC is unsatisfactory. In this study, we performed whole-exome sequencing (WES) of 23 hypopharyngeal tumor and paired adjacent normal tissue to identify novel candidate driver genes associated with hypopharyngeal carcinoma. We identified several copy number variants (CNVs) and 15 somatic mutation genes that were associated with hypopharyngeal carcinoma. Mutations in nine new genes (PRB4, NSD1, REC8, ZNF772, ZNF69, EI24, CYFIP2, NEFH, KRTAP4-5) were also indentified. PRB4 and NSD1 expression were significantly upregulated in hypopharyngeal carcinoma, which was confirmed in an independent cohort using IHC. There was a positive relationship between PRB4 and NSD1. Downregulation of PRB4 by siRNA could inhibit cell growth, colony formation and cell invasion. Notably, we here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter. In summary, we pinpoint the predominant mutations in hypopharyngeal carcinoma by WES, highlighting the substantial genetic alterations contributing to hypopharyngeal carcinoma tumorigenesis. We also indentify a novel epigenetically regulatory between PRB4 and NSD1 that contribute to hypopharyngeal carcinoma tumorigenesis. They may become potential prognostic biomarkers and therapeutic target for hypopharyngeal carcinoma treatment.


epigenetic; hypopharyngeal cancer; mutations; therapeutic target; whole-exome sequencing

Conflict of interest statement

CONFLICTS OF INTEREST No conflicts of interest exits in this study.

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