Molecular signatures in peripheral T-cell lymphoma (PTCL)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE19069 | GEO | 2010/02/08
SECONDARY ACCESSION(S): PRJNA120473
REPOSITORIES: GEO
Similar Datasets
Project description:Molecular signatures to improve diagnosis in PTCL and prognostication in angioimmunoblastic T-cell lymphoma (AITL). Gene expression profiling of PTCL patient samples was performed to investigate whether molecular signatures can be used to identify distinct entities of PTCL. Gene expression profiling was performed on PTCL and natural-killer cell lymphoma (NKCL) to define molecular classifiers for the more common entities of PTCL, to identify unique entities within PTCL-U, to elucidate unique tumor and microenvironmental interactions and oncogenic pathways in AITL, and to construct a molecular prognosticator for AITL.
2010-02-27 | E-GEOD-19069 | 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 (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.
2021-08-26 | GSE182769 | GEO
Project description:Mature NK and T-cell lymphomas are occasionally encountered in Asia but are very rare in Western populations. In part due to its rarity, little is known about this group of neoplasms, and despite being rather different disease entities, they are all treated similarly but with diverse clinical outcomes. Novel biomarkers (at both the genetic and protein levels) are needed to resolve diagnostic difficulties, improve prognostication and develop targeted therapies. To rectify this deficiency, we interrogated the transcriptome of several NK and mature T-cell lymphomas by whole-genome expression profiling for new markers that may further stratify this diverse group of conditions. Our initial efforts have identified a promising candidate marker that appears to differentiate NKTL lymphoma from other forms of T-cell neoplasms, and this finding has been validated by immunohistochemistry on archival material in a large number of patient cases. Correlating gene expression status with tumor type. Gene expression profiling was performed on 8 cases of angioimmunoblastic T-cell lymphoma (AITL), 4 cases of natural killer T-cell lymphoma (NKTL), and 6 cases of peripheral T-cell lymphoma - unspecified (PTCL-U). In addition, expression profiling was performed on one xenograft tumor, which was derived from a primary NKTL, and its cultured line.
2011-03-01 | E-GEOD-20874 | biostudies-arrayexpress
Project description:Somatic mutations in 3 AITL and 3 PTCL, not otherwise specified (PTCL-NOS) specimens were explored using whole-exome sequencing.
| EGAS00001000557 | EGA
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:Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression–based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis. We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays.
2023-02-23 | GSE225757 | GEO
Project description:Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression–based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis. We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays.
2023-02-23 | GSE225758 | GEO
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