RT Journal Article
SR Electronic
T1 Genome sequencing analysis identifies high-risk Epstein-Barr virus subtypes for nasopharyngeal carcinoma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 486613
DO 10.1101/486613
A1 Miao Xu
A1 Youyuan Yao
A1 Hui Chen
A1 Shanshan Zhang
A1 Tong Xiang
A1 Su-Mei Cao
A1 Zhe Zhang
A1 Bing Luo
A1 Zhiwei Liu
A1 Zilin Li
A1 Guiping He
A1 Qi-Sheng Feng
A1 Li-Zhen Chen
A1 Xiang Guo
A1 Weihua Jia
A1 Ming-Yuan Chen
A1 Bingchun Zhao
A1 Xiao Zhang
A1 Shang-Hang Xie
A1 Roujun Peng
A1 Ellen T. Chang
A1 Vincent Pedergnana
A1 Lin Feng
A1 Jin-Xin Bei
A1 Ruihua Xu
A1 Mu Sheng Zeng
A1 Weimin Ye
A1 Hans-Olov Adami
A1 Xihong Lin
A1 Weiwei Zhai
A1 Yi-Xin Zeng
A1 Jianjun Liu
YR 2018
UL http://biorxiv.org/content/early/2018/12/04/486613.abstract
AB Epstein-Barr virus (EBV) infection is ubiquitous worldwide and associated with multiple cancers including nasopharyngeal carcinoma (NPC). The role of EBV viral genomic variation in NPC development and its striking endemicity in southern China has been poorly explored. Through large-scale genome sequencing and association study of EBV isolates from China, we identified two non-synonymous EBV variants within BALF2 strongly associated with NPC risk (conditional P value 1.75×10-6 for SNP162476_C and 3.23×10-13 for SNP163364_T), whose cumulative effects contributed to 83% of the overall risk in southern China. Phylogenetic analysis of the risk variants revealed a unique origin in southern China followed by clonal expansion. EBV BALF2 haplotype carrying the risk variants were shown to reduce viral lytic DNA replication, as a result potentially promoting viral latency. Our discovery has not only provided insight to the unique endemic pattern of NPC occurrence in southern China, but also paved the way for the identification of individuals at high risk of NPC and effective intervention program to reduce the disease burden in southern China.