Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Fabio Fuligni
PROVIDER: E-GEOD-53633 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | Affymetrix HG-U133 Plus 2.0 : 7 NKTCL biopsies, 2 NKTCL cell lines (SNK6, SNT8), 16 PTCL NOS biopsies, 2 NK cells samples | Biopsies and cell lines of NK/T-cell lymphoma, nasal-type (NKTCL) were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared to PTCL, NOS, NKTCL had higher transcript levels for NK-cell markers and cytotoxic molecules, especially granzyme H, a novel sensitive biomarker of NKTCL. Compared to normal NK cells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, EBV-induced genes and PDGFRA. Notably, PDGFR? and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL-cell line was sensitive to imatinib. Deregulation of the AKT, JAKSTAT and NF-?B pathways suggested by bioinformatical analysis, was corroborated by nuclear expression of phosphorylated AKT, STAT3 and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 (1q44), IL6R (1q21.3), CCL2 (17q12), TNFRSF21 (6p12.3)). Several features of NKTCL uncovered by this analysis (overexpression of VEGFA and its receptor KDR by the tumor cells, overexpression of MET-HGF) suggest deregulation of angiogenic pathways. Integrative analysis also identified a novel putative tumor suppressor HACE1 in the frequently deleted 6q21 region. This study highlights emerging oncogenic pathways in NKTCL and identifies novel diagnostic and therapeutic targets. | Submitter : Aurelien de Reynies <reyniesa@ligue-cancer.fr> | Project leader : Philippe Gaulard <philippe.gaulard@hmn.aphp.fr>
2009-12-31 | E-TABM-702 | biostudies-arrayexpress
Project description:A ï¾Cartes dï¾Identite des Tumeursï¾ (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | Affymetrix HG-U133 Plus 2.0 : 17 AITL biopsies, 2 AITL sorted cells, 16 PTCL NOS biopsies | The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell- and follicular dendritic cell-related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (T(FH)) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published T(FH)-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several T(FH) genes was validated by immunohistochemistry in AITLs. A few cases with molecular T(FH)-like features were identified among CD30(-) PTCLs-u. Our findings strongly support that T(FH) cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30(-) PTCLs-u may derive from or be related to AITL.| Submitter : Aurelien de Reynies <reyniesa@ligue-cancer.fr> | Project leader : Philippe Gaulard <philippe.gaulard@hmn.aphp.fr>
2009-09-22 | E-TABM-783 | biostudies-arrayexpress
Project description:Peripheral T-cell lymphoma unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and dismal prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T-cells. Comparison with the profiles of purified T-cell subpopulations [CD4+, CD8+, resting (HLA-DR-), and activated (HLA-DR+)] reveals that PTCLs/U are most closely related to activated peripheral T-lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T-cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g. apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic or stromal location. Among others, PTCLs/U aberrantly express PDGFRA, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRA and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone-deacetylase) are found. These results, which might be extended to other rarer PTCL categories, are provided with implications for tumor pathogenesis and clinical management. Experiment Overall Design: 40 cases of Peripheral T-cell lymphoma (PTCL) were analyzed, including 28 PTCL/unspecified, 6 angioimmunoblastic (AITL) and 6 anaplastic large cell lymphoma cases (ALCL). Frozen lymph-nodes collected at diagnosis (before therapy) were used. In addition, 20 samples of normal T-cells (5 CD4+, 5 CD8+, 5 HLA-DR+, and 5 HLA-DR-) collected from peripheral blood and tonsils of healthy donors were studied. The HG U133 2.0 plus microarray (Affymetrix) was adopted.
2008-06-14 | E-GEOD-6338 | biostudies-arrayexpress
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 manufacturer´s protocol.
2010-03-17 | E-GEOD-15842 | biostudies-arrayexpress
Project description:Genome-wide analysis of nodal peripheral T-cell lymphomas (PTCL/NOS, AITL and ALCL) was used to identify molecular signatures corresponding to different subgroups. We also aimed to define the counterparts of PTCLs/NOS based on their global gene expression profiles. We developed a new molecular classifier able to distinct PTCL/NOS heterogeneity due to the correspondence to different counterparts.
2018-12-21 | GSE45712 | 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.
2021-08-26 | GSE182769 | GEO
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
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: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
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.
2013-12-25 | GSE53633 | GEO