Format

Send to

Choose Destination
Carcinogenesis. 2018 Dec 31;39(12):1517-1528. doi: 10.1093/carcin/bgy108.

Identification of genomic alterations in nasopharyngeal carcinoma and nasopharyngeal carcinoma-derived Epstein-Barr virus by whole-genome sequencing.

Tu C1,2,3, Zeng Z1,2,3, Qi P2, Li X3, Guo C1,2,3, Xiong F1, Xiang B1,2,3, Zhou M1,2,3, Liao Q2,4, Yu J4, Li Y2,5, Li X1,2,3, Li G1,2,3, Xiong W1,2,3.

Author information

1
The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.
2
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, Hunan, China.
3
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
4
Department of Head and Neck Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
5
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

Abstract

Nasopharyngeal carcinoma (NPC) is a common tumor in southern China with marked ethnic and geographic distributions and concomitant Epstein-Barr virus (EBV) infection. However, the molecular basis of NPC remains largely unknown, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. Whole-genome sequencing of a collection of 12 EBV-positive paired NPC tumor/peripheral blood samples from Hunan Province was performed, and the FBXO11 gene was subjected to further functional analyses. We identified 69 missense mutations in signaling pathways typically altered in cancer, including NF-κB and Wnt/Hedgehog/Notch. Additionally, 122 variations were identified in non-coding regions. Among these, a subset of genes was confirmed as dysregulated in NPC by mining the NPC cDNA microarray database. The randomly selected gene, FBXO11, could promote the malignant progression of NPC in vitro. Full-length EBV genomes from 8 of the 12 patients with NPC were also successfully assembled, and latent EBV infection is a primary cause of NPC. The various subtypes of EBV detected exhibited clear correlations with its geographical distribution. This study has explored novel biological markers and tumorigenic pathways with substantial potential to enhance therapeutic strategies for NPC.

PMID:
30102338
DOI:
10.1093/carcin/bgy108
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center