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Minimal Genomic Instability and Increased Immune Activity Differentiate EBV-positive PTCL from ENKTL and PTCL NOS [GEP]

ABSTRACT: The molecular biology of the primary nodal EBV-positive variant of PTCL (PTCL-EBV) and its relationship with extranodal NK/T-cell lymphoma (ENKTL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) remains poorly understood. In this study, we assessed the relationship between the three diseases using gene and EBV miRNA expression profiling, and copy number aberration (CNA) analyses and attempted to characterize the degree of genomic instability (GI). This series is the GEP data of 84 cases of FFPE NKTL samples and 4 cases of Lymph node controls.

ORGANISM(S): Homo sapiens

PROVIDER: GSE160119 | GEO | 2021/11/27

REPOSITORIES: GEO

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Minimal Genomic Instability and Increased Immune Activity Differentiate EBV-positive PTCL from ENKTL and PTCL NOS [CNA]

Project description:The molecular biology of the primary nodal EBV-positive variant of PTCL (PTCL-EBV) and its relationship with extranodal NK/T-cell lymphoma (ENKTL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) remains poorly understood. In this study, we assessed the relationship between the three diseases using gene and EBV miRNA expression profiling, and copy number aberration (CNA) analyses and attempted to characterize the degree of genomic instability (GI). This series is the oncoscan CNA data of 77 NKTL samples.

2021-11-27 | GSE160118 | GEO

Minimal Genomic Instability and Increased Immune Activity Differentiate EBV-positive PTCL from ENKTL and PTCL NOS [GEP]

Project description:Minimal Genomic Instability and Increased Immune Activity Differentiate EBV-positive PTCL from ENKTL and PTCL NOS [GEP]

| PRJNA672042 | ENA

Minimal Genomic Instability and Increased Immune Activity Differentiate EBV-positive PTCL from ENKTL and PTCL NOS

Project description:Minimal Genomic Instability and Increased Immune Activity Differentiate EBV-positive PTCL from ENKTL and PTCL NOS

| PRJNA672033 | ENA

Minimal Genomic Instability and Increased Immune Activity Differentiate EBV-positive PTCL from ENKTL and PTCL NOS [CNA]

Project description:Minimal Genomic Instability and Increased Immune Activity Differentiate EBV-positive PTCL from ENKTL and PTCL NOS [CNA]

| PRJNA672043 | ENA

High-throughput sequence analysis of peripheral T-cell lymphomas indicates subtype specific viral gene expression patterns and immune cell microenvironments

Project description:Certain peripheral T-cell lymphomas (PTCLs) have been associated with viral infection, particularly infection with Epstein-Barr virus (EBV). However, a comprehensive virome analysis across PTCLs has not previously been reported, and viral gene expression profiles have been studied only in certain PTCL subtypes. In this study we utilized published RNA-seq data sets from seven different PTCL studies as well as new RNA-seq data from our laboratory to screen for virus association, to analyze viral gene expression, and to assess B- and T-cell receptor diversity paradigms across these tumor types. In addition to identifying EBV in angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T cell lymphoma (ENKTL), two PTCL subtypes with well-established EBV associations, we also detected EBV in several cases of anaplastic large cell lymphoma (ALCL), and we found evidence of infection by the oncogenic viruses KSHV and HTLV-1 in isolated PTCL cases. In AITLs, EBV gene expression analysis showed expression of immediate early, early and late lytic genes, suggesting either abortive lytic replication and/or productive infection in a subset of the EBV infected infiltrating B-lymphocytes. Deconvolution of immune cell subpopulations demonstrated a greater B-cell signal in AITLs than in other PTCL subtypes, consistent with a larger role for B-cell support in the pathogenesis of AITL. T-cell receptor (TCR) and B-cell receptor (BCR) repertoires reconstructed from RNA-seq data demonstrated increased BCR diversity in AITLs, consistent with a possible EBV-driven polyclonal response. These findings indicate potential alternative roles for EBV in PTCLs in addition to the canonical oncogenic mechanisms associated with EBV latent infection. The findings also suggest the involvement of other viruses in T-cell lymphoma pathogenesis and demonstrate immunological alterations associated with these cancers.

2019-06-25 | GSE131261 | GEO

DNMT3A mutations define a unique biological and prognostic subgroup associated with cytotoxic T-cells in PTCL-NOS [RNA-Seq]

Project description:Peripheral T-cell lymphomas (PTCLs) are heterogenous T-cell neoplasms often associated with epigenetic dysregulation. We investigated de novo DNA methyltransferase 3A (DNMT3A) mutations in common PTCL entities, including angioimmunoblastic T-cell lymphoma and novel molecular subtypes identified within PTCL-not otherwise specified (PTCL-NOS) designated as PTCL-GATA3 and PTCL-TBX21. DNMT3A-mutated PTCL-TBX21 cases showed inferior overall-survival, with DNMT3A mutated residues skewed towards the methyltransferase domain and dimerization motif (S881–R887). Transcriptional profiling demonstrated significant enrichment of activated CD8+ T-cell cytotoxic gene signatures in the DNMT3A-mutant PTCL-TBX21 cases, which was further validated using immunohistochemistry. Genome-wide methylation analysis of DNMT3A-mutant versus wild-type PTCL-TBX21 cases demonstrated hypomethylation in target genes regulating IFN-g, TCR signaling and EOMES, a master transcriptional regulator of cytotoxic effector cells. Similar findings were observed in a murine model of PTCL with Dnmt3a loss (in-vivo) and further validated in-vitro by ectopic expression of DNMT3A-mutants (DNMT3A-R882, -Q886, -V716, versus WT) in CD8+T-cell line, resulting in T-cell activation and EOMES upregulation. Furthermore, stable, ectopic expression of the DNMT3A-mutants in primary CD3+ T-cell cultures resulted in the preferential outgrowth of CD8+ T-cells with DNMT3AR882H mutation. Single-cell-RNA-seq analysis of CD3+ T-cells revealed differential CD8+ T-cell subset polarization, mirroring findings in DNMT3A-mutated PTCL-TBX21 and validating the cytotoxic and T-cell memory transcriptional programs associated with the DNMT3AR882H mutation. Our findings indicate that DNMT3A mutations define a cytotoxic subset in PTCL-TBX21 with prognostic significance, thus may further refine pathological heterogeneity in PTCL-NOS and suggest alternative treatment strategies for this subset.

2022-05-29 | GSE204876 | GEO

DNMT3A mutations define a unique biological and prognostic subgroup associated with cytotoxic T-cells in PTCL-NOS [meDIP-Seq]

2022-05-29 | GSE204875 | GEO

SNP array genomic profiling of PTCL NOS

Project description:DNA extracted from frozen tissue of 47 peripheral T-cell lymphomasânot otherwise specified [PTCL-NOS] was hybridized to 250k StyI SNP arrays 47 PTCL NOS compared to healthy reference DNA. DNA of PTCL NOS was extracted from frozen tissue blocks, DNA of healthy individual was extracted from peripheral blood mononuclear cells. Array hybridization was performed according to manufacturerÂ´s protocol.

2010-03-17 | E-GEOD-15842 | biostudies-arrayexpress

RNA sequencing of PTCL-NOS

Project description:To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we performed RNA-sequencing of 15 cases. We describe a recurrent FYN-TRAF3IP2 fusion transcript in PTCL-NOS and PTCL-TFH and a KHDRBS1-LCK fusion transcript in PTCL-NOS.

| EGAS00001005015 | EGA

SNP array genomic profiling of PTCL NOS

Project description:DNA extracted from frozen tissue of 47 peripheral T-cell lymphomas–not otherwise specified [PTCL-NOS] was hybridized to 250k StyI SNP arrays

2010-03-17 | GSE15842 | GEO

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