Peripheral T-cell Lymphoma gene expression profiling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE132550 | GEO | 2019/09/19
REPOSITORIES: GEO
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Project description:Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P=.01). High expression of cytotoxic genesignaturewithin the TBX21 subgroup also showed poor clinical outcome (P=.05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P=.004).
2015-06-01 | GSE58445 | GEO
Project description:Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of around 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma, AITL; PTCL-with T follicular helper phenotype, PTCL-TFH; PTCL-not otherwise signified, PTCL-NOS) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH and PTCL-NOS. The main differences between the three nodal PTCL classes involved the RHOAG17V mutations (p<0.0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases, but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these three categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL.
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Project description:Identification of the determinants of PDGFRA activity in PTCL/NOS (Peripheral T-cell lymphoma/not otherwise specified) and to elucidate the biological consequences of its activation. We generated GEP from samples of primary PTCL/NOS cells treated or not with imatinib mesylate (see below) as well as from EOL1 cells (3 samples each)
2013-12-25 | E-GEOD-53633 | biostudies-arrayexpress
Project description:Identification of the determinants of PDGFRA activity in PTCL/NOS (Peripheral T-cell lymphoma/not otherwise specified) and to elucidate the biological consequences of its activation.
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Project description:We evaluate differential gene expression in 6 cases of canine CD4+ peripheral T-cell lymphoma (PTCL) compared to sorted CD4+ lymphocytes from the lymph nodes of healthy dogs.Lymph node aspirates from 6 dogs submited for routine diagnostics and diagnosed with CD4+ PTCL by flow cytometry were selected for RNA-seq. Patients were naïve to treatment at the time of sample submission. Aspirates from selected cases had a purity of greater than 88% neoplastic cells. Neoplastic cells were identified by the following immunophenotype: CD4+CD3+CD5+/-CD45+MHCIIlo. Hierarchical clustering of samples resulted in distinct separation of control lymphocytes and PTCL cases with intermixing of PTCL from Boxer and non-Boxer dogs. Top enriched pathways are involved in G-coupled protein receptor signaling, extracellular matrix remodeling and vascular development, inflammatory response and immune signaling, and mitotic activity. This study provides the global gene expression analysis of aggressive canine T-cell lymphoma using RNAsequencing.
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Project description:Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T-Cell lymphoma/leukemia, peripheral T-cell lymphoma, not otherwise specified, and mantle cell lymphoma (MCL). Our analysis was extended to other types of lymphoma including marginal zone lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL). We examined the results of array comparative genomic hybridization analysis for 332 cases to determine if clonal heterogeneity existed in each case. Results showed that frequencies of clonal heterogeneity varied from 25% to 69% among different types of lymphoma. Multivariate analysis indicated that MCL and DLBCL with clonal heterogeneity showed a significantly poorer prognosis. Interestingly, 9p21.3 (CDKN2A/ 2B) loss and 17p13 (TP53, ATP1B2, SAT2, SHBG) loss were common regions among various types of lymphoma with clonal heterogeneity, suggesting at least in part that loss of these genes may play a role in clonal heterogeneity. We analyzed previously untreated 332 cases of lymphoma (comprising 29 cases of mantle cell lymphoma, 117 cases of diffuse large B-cell lymphoma (DLBCL), 79 cases of Follicular lymphoma, 24 cases of Burkitt lymphoma, 31 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, and 51 peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)).
2014-04-01 | E-GEOD-54303 | biostudies-arrayexpress
Project description:Peripheral T cell lymphoma (PTCL) is a very aggressive disease which currently lacks efficient targeted therapy. New therapeutic strategies are needed to improve the very poor outcome of these patients. However, little is known about the molecular pathogenesis of this disease. In this study, we performed a gene expression profiling analysis of a series of 38 PTCL cases in order to find deregulated pathways or genes that could become therapeutic agents for PTCL patients. 38 PTCL cases and 6 reactive lymph nodes were hybridized with the Universal Human Reference RNA (Stratagene, La Jolla, CA), which served as the reference sample.
2012-07-31 | E-GEOD-36172 | biostudies-arrayexpress
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 GEP data of 84 cases of FFPE NKTL samples and 4 cases of Lymph node controls.
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Project description:Peripheral T cell lymphoma (PTCL) is a very aggressive disease which currently lacks efficient targeted therapy. New therapeutic strategies are needed to improve the very poor outcome of these patients. However, little is known about the molecular pathogenesis of this disease. In this study, we performed a gene expression profiling analysis of a series of 38 PTCL cases in order to find deregulated pathways or genes that could become therapeutic agents for PTCL patients.
2012-08-01 | GSE36172 | GEO
Project description:Peripheral T cell lymphoma (PTCL) is a heterogeneous group of hematological cancers arising from the malignant transformation of mature T cells. In a cohort of 28 PTCL cases, we identified recurrent overexpression of MYCN, a member of the MYC family of oncogenic transcription factors. Approximately half of all PTCL cases was characterized by a MYC expression signature. Inducible expression of MYCN in lymphoid cells in a mouse model caused T cell lymphoma that recapitulated human PTCL with a MYC expression signature. Integration of mouse and human expression data identified EZH2 as a key downstream target of MYCN. Remarkably, EZH2 was found to be an essential co-factor for the transcriptional activation of the MYCN-driven gene expression program, which was independent of methyltransferase activity, but dependent on phosphorylation by CDK1. MYCN-driven T cell lymphoma was sensitive to EZH2 degradation or CDK1 inhibition, which displayed synergy with FDA-approved HDAC inhibitors.
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