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

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

PROVIDER: PRJNA672033 | ENA |

REPOSITORIES: ENA

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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.

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

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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]

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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]

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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.

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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

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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.

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SMARCB1 loss defines a novel PTCL-NOS subtype displaying an immunosuppressive TME susceptible to HDAC inhibitors [bulk RNA-seq]

Project description:Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) are aggressive and heterogeneous tumors with poor outcome and scarce genetic characterization. We analyzed by immunohistochemistry tumor tissue of adult and pediatric PTCL-NOS patients and discovered frequent loss of SMARCB1 positivity, mostly associated with pediatric cases (45%). Using a genetically engineered mouse model (PTCL-NOSSmarcb1-) and single-cell RNA sequencing, we investigated the transcriptional landscape of this Smarcb1-negative PTCL-NOS tumor and the functional interactions between tumor and tumor microenvironment (TME). We unrevealed an immunosuppressive, exhausted and proinflammatory TME, characterized by high myeloid cell infiltration (predominantly myeloid derived suppressor cells, MDSC) and reduced lymphoid infiltration. In addition, using a multidrug epigenetic screen in vitro, we identified histone deacetylase inhibitors (HDACi) as promising agents against PTCL-NOSSmarcb1-. Treatment of PTCL-NOSSmarcb1- mice with SAHA, a pan-HDACi, triggered TME remodelling, promoting the replenishment of T- and B-cell compartments and the limitation/reversion of the exhaustion phenotype. In conclusion, we have identified a novel PTCL-NOS subtype characterized by the loss of SMARCB1 at pediatric ages, presenting an exhausted and immunosuppressive TME. Administration of SAHA reshaped the TME increasing lymphoid cells recruitment into the tumor bed, turning the tumor from cold to hot. These results provide the rationale for further investigations based on combination therapies.

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SMARCB1 loss defines a novel PTCL-NOS subtype displaying an immunosuppressive TME susceptible to HDAC inhibitors [single-cell RNA-seq]

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-11-27 | GSE160120 | GEO