Transcriptional profiling of Epstein–Barr virus (EBV) genes and host cellular genes in nasal NK/T-cell lymphoma and chronic active EBV infection

• Published in: British journal of cancer 2006-02, Vol.94 (4), p.599-608
• Main Authors: Zhang, Y, Ohyashiki, J H, Takaku, T, Shimizu, N, Ohyashiki, K
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; BZLF1 protein; Cancer; Cancer Research; Chronic Disease; Chronic infection; Cyclin-dependent kinase 2; Disease Progression; DNA microarrays; double prime T-cell lymphoma; Drug Resistance; Epidemiology; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Genetics and Genomics; Herpes viruses; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - pathogenicity; Humans; Immediate-early proteins; Immunoproliferative diseases; Infections; Interleukin 1; Internet; Killer Cells, Natural; Lymphocytes T; Lymphoma; Lymphoma, T-Cell - pathology; Lymphoma, T-Cell - virology; Medical research; Medical sciences; Molecular Medicine; Nose Neoplasms - pathology; Nose Neoplasms - virology; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Oncology; Pathogenesis; T-cell lymphoma; Transcription; Tumor Cells, Cultured; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602968

Nasal NK/T-cell lymphoma is an aggressive subtype of non-Hodgkin lymphoma (NHL) that is closely associated with Epstein–Barr virus (EBV). The clonal expansion of EBV-infected NK or T cells is also seen in patients with chronic active EBV (CAEBV) infection, suggesting that two diseases might share a partially similar mechanism by which EBV affects host cellular gene expression. To understand the pathogenesis of EBV-associated NK/T-cell lymphoproliferative disorders (LPD) and design new therapies, we employed a novel EBV DNA microarray to compare patterns of EBV expression in six cell lines established from EBV-associated NK/T-cell LPD. We found that expression of BZLF1, which encodes the immediate-early gene product Zta, was expressed in SNK/T cells and the expression levels were preferentially high in cell lines from CAEBV infection. We also analyzsd the gene expression patterns of host cellular genes using a human oligonucleotide DNA microarray. We identified a subset of pathogenically and clinically relevant host cellular genes, including TNFRSF10D, CDK2, HSPCA, IL12A as a common molecular biological properties of EBV-associated NK/T-cell LPD and a subset of genes, such as PDCD4 as a putative contributor for disease progression. This study describes a novel approach from the aspects of viral and host gene expression, which could identify novel therapeutic targets in EBV-associated NK/T-cell LPD.