Abstract 3425: Whole-transcriptome analyses of EBV-associated nasopharyngeal carcinoma using next-generation transcriptome sequencing
| Autor: | Grace Tin-Yan Chung, Ken Kai-Yuen Tso, Sai Wah Tsao, Siu Tim Cheung, Philippe Busson, Kevin Y. Yip, Cathy Ka-Yan Mak, Ka Fai To, Sau Dan Lee, Kwok Wai Lo |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Cancer Research. 74:3425-3425 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2014-3425 |
| Popis: | Nasopharyngeal carcinoma (NPC) is unique among epithelial cancers arising from the head and neck regions. This specific cancer type is consistently associated with EBV infection. Using RNA-seq, we have conducted a comprehensive assessment of EBV and cellular gene expression in six NPC cell line and patient-derived xenografts (PDXs). In these tumor lines, expression of EBV latent genes including EBNA1, LMP1, LMP2A and BamH1 A transcripts was quantitated. Among the viral genes, the BamH1 A transcripts were detected as the major transcripts with various splicing variants. Expression of these transcripts in NPC was further validated by qRT-PCR analysis. Active lytic gene expression and lytic viral replication was not observed in these tumor lines. Analysis of the RNA-seq data has identified multiple fusion transcripts. A total of 18 candidate fusions were validated in these tumor lines. A novel fusion transcript, UBR5-ZNF423 was detected in C666-1 cells and 8.3% of primary tumors. The transcript produces a chimeric fusion protein which might alter the function of EBF transcription factor. A significant growth inhibitory effect was observed in UBR5-ZNF423 knockdown C666-1 cells. Constitutive expression of UBR5-ZNF423 fusion in NIH3T3 cells induced in vivo tumor formation in nude mice model. The findings strongly suggest that the fusion gene play a causative role in NPC tumorigenesis. Using the expression profile of immortalized nasopharyngeal epithelial cells as control, our study also revealed the differential expression of cellular genes and specific alternative spliced transcripts in NPC. Significant upregulation of genes involved in cytokine-cytokine receptor interaction (e.g. CCL5, CCL20, CXCL10, CXCR4, IL2RG) was consistently detected in the tumor lines. Most of them were targets of the NF-kappaB signaling pathways, which are constitutively activated in EBV-associated NPC. In addition, the analyses also discovered several potential druggable targets (e.g. CD74) and oncogenic non-coding RNAs (e.g. AFAP1-AS1) in NPC, which may contribute to the development of new therapeutic strategies for this cancer. The whole-transcriptome analyses greatly enhance our understanding of the molecular basis of EBV-infected NPC. Citation Format: Cathy Ka-Yan Mak, Grace Tin-Yan Chung, Kevin Yuk-Lap Yip, Ken Kai-Yuen Tso, Sau-Dan Lee, Siu-Tim Cheung, Sai-Wah Tsao, Pierre Busson, Ka-Fai To, Kwok-Wai Lo. Whole-transcriptome analyses of EBV-associated nasopharyngeal carcinoma using next-generation transcriptome sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3425. doi:10.1158/1538-7445.AM2014-3425 |
| Databáze: | OpenAIRE |
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