DOI: 10.1101/486613Dec 4, 2018Paper

Genome sequencing analysis identifies high-risk Epstein-Barr virus subtypes for nasopharyngeal carcinoma

BioRxiv : the Preprint Server for Biology
Miao XuJianjun Liu

Abstract

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 X 10-6 for SNP162476\_C and 3.23 X 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.

Related Concepts

Cell Growth
Epstein-Barr Virus
Viral Genome
Mandibular Right Second Primary Molar
Multiple Malignancy
Subtype (Attribute)
Intervention Program
Comparative Genomic Analysis
Genome Sequencing
BALF2 protein, Human herpesvirus 4

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