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Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice [training]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE225757 | GEO | 2023/02/23

REPOSITORIES: GEO

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Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice [validation]

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

Diagnostic performance of transcriptomic signatures for the evaluation of suspected tuberculosis in routine clinical practice

Project description:Background: Blood transcriptomic signatures for diagnosis of tuberculosis (TB) have shown promise in case-control studies but their diagnostic accuracy has not been prospectively validated in adults presenting with the full clinical spectrum of suspected TB, including extra-pulmonary TB, and its associated differential diagnoses with concomitant latent TB infection. Methods: Our study was nested within a prospective multi-center cohort study in secondary care in England. Patients had whole-blood taken for microarray to measure abundance of 47,275 transcripts and interferon-gamma release assays (IGRAs) at clinical presentation with suspected TB and were followed up for 6-12 months’ to determine final diagnoses based on pre-defined diagnostic criteria. The diagnostic accuracy of published transcriptomic signatures and a novel cohort-derived signature were assessed to generate area under the receiver-operating characteristic curves (AUC), sensitivities and specificities.

2021-01-26 | GSE144127 | GEO

Transcription profiling of biopsy samples from peripheral T-cell lymphoma (PTCL)

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

Molecular signatures in peripheral T-cell lymphoma (PTCL)

2010-02-08 | GSE19069 | GEO

Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma

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

Gene expression data of formalin-fixed-paraffin-embedded (FFPE) renal biopsy tissue assessed with Banff Human Organ Transplant (B-HOT) gene panel assay on NanoString nCounter®

Project description:Development and validation of a multi-class molecular model for differential diagnosis of renal allograft rejection, built upon gene expression data from the B-HOT gene panel in a large and diverse cohort of diagnostic FFPE renal biopsies.

2023-12-12 | GSE212160 | GEO

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

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.

2021-11-27 | GSE160119 | 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

Molecular signatures in natural-killer (NK) cell lymphoma

Project description:NK-cell lymphoma shares strikingly similar molecular features with a distinct subset of gamma-delta T-cell lymphoma. Gene expression profiling of NK-cell lymphoma patient samples was performed to investigate whether molecular signatures can be used to identify entities of peripheral T-cell lymphoma (PTCL) with NK-cell-like features.

2010-03-18 | GSE19067 | GEO

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