Dataset Information

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

ABSTRACT: 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 analyzed 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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC2361178 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zhang Y Y Ohyashiki J H JH Takaku T T Shimizu N N Ohyashiki K K

British journal of cancer 20060201 4

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, ...[more]

PMID: 16449999

Similar Datasets

Project description:BackgroundNK/T cell lymphoma is an aggressive lymphoma almost always associated with EBV. BamHI-A rightward open reading frame 1 (BARF1) and BamHI-H rightward open reading frame 1 (BHRF1) are two EBV early genes, which may be involved in the oncogenicity of EBV. It has been found that V29A strains, a BARF1 mutant subtype, showed higher prevalence in NPC, which may suggest the association between this variation and nasopharyngeal carcinoma (NPC). To characterize the sequence variation patterns of the Epstein-Barr virus (EBV) early genes and to elucidate their association with NK/T cell lymphoma, we analyzed the sequences of BARF1 and BHRF1 in EBV-positive NK/T cell lymphoma samples from Northern China.MethodsIn situ hybridization (ISH) performed for EBV-encoded small RNA1 (EBER1) with specific digoxigenin-labeled probes was used to select the EBV positive lymphoma samples. Nested-polymerase chain reaction (nested-PCR) and DNA sequence analysis technique were used to obtain the sequences of BARF1 and BHRF1. The polymorphisms of these two genes were classified according to the signature changes and compared with the known corresponding EBV gene variation data.ResultsTwo major subtypes of BARF1 gene, designated as B95-8 and V29A subtype, were identified. B95-8 subtype was the dominant subtype. The V29A subtype had one consistent amino acid change at amino acid residue 29 (V → A). Compared with B95-8, AA change at 88 (L → V) of BHRF1 was found in the majority of the isolates, and AA79 (V → L) mutation in a few isolates. Functional domains of BARF1 and BHRF1 were highly conserved. The distributions of BARF1 and BHRF1 subtypes had no significant differences among different EBV-associated malignancies and healthy donors.ConclusionThe sequences of BARF1 and BHRF1 are highly conserved which may contribute to maintain the biological function of these two genes. There is no evidence that particular EBV substrains of BARF1 or BHRF1 is region-restricted or disease-specific.

Project description:Extranodal natural killer/T cell lymphoma-nasal type (EN-NK/T-NT) is extremely rare in Western countries; however, it is the most common subtype of peripheral T cell lymphoma in China. Despite this, there are a limited number of clinicopathological research studies on Epstein-Barr virus (EBV)-negative EN-NK/T-NTs. EBV-negative EN-NK/T-NT is a rare disease type, which has not been fully investigated. If other diagnostic criteria are met, such as the lesions being located predominantly in the upper aerodigestive tract, the presence of angiocentricity or angioinvasion, necrosis and expression of NK/T-cell phenotype, EN-NK/T-NT may be diagnosed, even if EBV is negative. In the present study, 99 cases of EN-NK/T-NTs were analyzed retrospectively, among which seven cases were EBV-negative EN-NK/T-NTs and selected for further investigation. In addition, the present study reviewed previously published research into EN-NK/T-NT, highlighting that EBV-negative EN-NK/T-NT is rare and that its geographical distribution is mainly in countries in Asia, Central America and South America. Patients with EBV-negative EN-NK/T-NT were all of Chinese ethnicity, with a median age of 32 years and primarily female. Furthermore, these patients shared similar clinicopathological characteristics (such as the tumor occurring mainly in the upper aerodigestive tract, the presence of vascular destruction, necrosis and cytotoxic phenotypes) to patients with EBV-positive EN-NK/T-NT. Immunohistochemistry and molecular analysis results indicated that tumor cells were primarily of NK or cytotoxic T origin; however, EBV-encoded small RNAs were not detected in any of these cases. Among the immunochemistry markers, T-bet was statistical significantly different between EBV-positive and -negative cases. Fluorescence in situ hybridization was also performed in two EBV-negative cases, including one case with a co-deletion of 6q21 and PR/SET domain 1 genes. There was only available follow-up data in 3/5 patients who survived for 37–113 months (median, 40 months). As EN-NK/T-NT can be diagnosed, even when EBV is negative, awareness of this subtype may prevent misdiagnosis or delayed diagnosis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets