Comparative genomic hybridization by array of genomic DNA from 18 cases of EBV+ DLBCL, 21 cases of EBV- DLBCL, and 13 cases of nonneoplastic tonsillar tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Heart, Spleen, Brain, Tongue, Tonsil, Lung, Lymph Node, Colon, Gastrointestinal System, Animal Ovary, Caecum
DISEASE(S): Epstein-barr Virus Positive,Epstein-barr Virus Negative
SUBMITTER: 
Heejei Yoon
PROVIDER: E-MTAB-1971 | ArrayExpress | 2014-02-01
REPOSITORIES: ArrayExpress
Dataset's files
primary
| Action | DRS | |||
|---|---|---|---|---|
| E-MTAB-1971.idf.txt | Idf | |||
| E-MTAB-1971.processed.1.zip | Processed | |||
| E-MTAB-1971.processed.2.zip | Processed | |||
| E-MTAB-1971.raw.1.zip | Raw | |||
| E-MTAB-1971.raw.2.zip | Raw |
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Project description:Copy number analysis was performed on EBV+ DLBCL samples compared with EBV- DLBCL. We analyzed the genomic DNA from 18 cases of EBV+ DLBCL, 21 cases of EBV- DLBCL, and 13 cases of nonneoplastic tonsillar tissues using OncoScan FFPE Express 2.0 (MIP). No technical replication were done.
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Project description:OBJECTIVE:Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV-pos DLBCL) is a recently identified entity. Data regarding outcome to frontline immuno-chemotherapy are conflicting. Although the prognostic impact of the tumour microenvironment (TME) in EBV-neg DLBCL is well-established, it remains untested whether the TME influences survival in EBV-pos DLBCL. There are no data with new digital gene expression technologies that simultaneously interrogate the virus, B cells and the tumour microenvironment (TME). METHODS:We used the NanoString™ platform in a population-based cohort of 433 patients to establish if the technology could detect EBV in the tumour biopsies and to investigate the influence that EBV has on the complex tumour microenvironment of DLBCL. RESULTS:Incidence of EBV-pos DLBCL was 6.9% with 5-year survival of 65% vs 82% in EBV-neg DLBCL (P = 0.018). EBV-pos tissues had similar expression of T-cell genes compared to EBV-neg DLBCL but higher levels of the antigen-presenting molecule B2M. This was countered by elevated PD-L1, PD-L2, LAG3 and TIM3 immune checkpoints and a higher CD163/CD68 "M2" macrophage score. CONCLUSION:In EBV-pos DLBCL, the TME is immuno-tolerogenic and may explain the poor outcomes seen in this subtype of DLBCL.
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Project description:Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare type of lymphoma with a high incidence in elderly patients, poor drug response, and unfavorable prognosis. Despite advances in genomic profiling and precision medicine in DLBCL, EBV+ DLBCL remain poorly characterized and understood. We include 236 DLBCL patients for EBV-encoded mRNA (EBER) <i>in situ</i> hybridization detection and analyzed 9 EBV+ and 6 EBV negative cases by next-generation sequencing (NGS). We then performed fluorescence <i>in situ</i> hybridization (FISH) and immunohistochemistry (IHC) to analyze chromosome rearrangements and gene expressions in 22 EBV+ and 30 EBV negative cases. The EBER results showed a 9.3% (22/236) positive rate. The NGS results revealed recurrent alterations in <i>MYC</i> and <i>RHOA</i>, components of apoptosis and NF-κB pathways. The most frequently mutated genes in EBV+ DLBCL were <i>MYC</i> (3/9; 33.3%), <i>RHOA</i> (3/9; 33.3%), <i>PIM1</i> (2/9; 22.2%), <i>MEF2B</i> (2/9; 22.2%), <i>MYD88</i> (2/9; 22.2%), and <i>CD79B</i> (2/9; 22.2%) compared with <i>KMT2D</i> (4/6; 66.7%), <i>CREBBP</i> (3/6; 50.0%), <i>PIM1</i> (2/6; 33.3%), <i>TNFAIP3</i> (2/6; 33.3%), and <i>BCL2</i> (2/6; 33.3%) in EBV-negative DLBCL. <i>MYC</i> and <i>KMT2D</i> alterations stood out the most differently mutated genes between the two groups. FISH detection displayed a lower rearrangement rate in EBV+ cohort. Furthermore, KMT2D expression was highly expressed and associated with poor survival in both cohorts. MYC was only overexpressed and related to an inferior prognosis in the EBV+ DLBCL cohort. In summary, we depicted a distinct mutation profile for EBV+ and EBV-negative DLBCL and validated the differential expression of KMT2D and MYC with potential prognostic influence, thereby providing new perspectives into the pathogenesis and precision medicine of DLBCL.
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