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.
Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma.
Sex, Age, Specimen part
View SamplesNK-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.
Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro.
Sex, Age, Specimen part
View SamplesPeripheral 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).
Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesAnaplastic Large Cell Lymphoma (ALCL) is a clinical and biological heterogeneous disease including ALK positive and ALK negative systemic forms. To discover biomarkers and/or genes involved in ALK negative ALCL pathogenesis, we applied the Cancer Outlier Profile Analysis (COPA) algorithm to a gene expression profiling data set including 249 cases of T-NHLs and normal T-cells. Ectopic co-expression of ERBB4 and COL29A1 genes was detected in 24% of ALK negative ALCL patients. RNA sequencing and 5'RNA Ligase Mediated Rapid Amplification of cDNA Ends (RLM-RACE) identified two novel ERBB4 truncated transcripts, displaying intronic Transcription Starting Sites. ERBB4 expression was confirmed at protein level by western blotting and immunohistochemistry. Moreover, by luciferase assays we defined that the expression of ERBB4 aberrant transcripts is promoted by endogenous intronic Long Terminal Repeats (LTRs). In conclusion, we identified a new subclass of ALK negative ALCL characterized by aberrant expression of ERBB4 truncated transcripts carrying intronic 5'UTRs.
Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts.
Specimen part
View SamplesSince follicular lymphoma (FL) grade 3A often coexist with a FL1/2 component a linear progression model of FL1, FL2 and FL3A has been developed. FL3B, on the other hand, is supposed to be more closely related to diffuse large B-cell lymphoma (DLBCL) and both FL3B and DLBCL are often simultaneously present in one tumor (DLBCL/FL3B).
Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis.
Sex, Age
View SamplesThe pathogenesis of diffuse large B cell lymphomas (DLBCL) is only partly understood. We analyzed 148 DLBCL by high resolution single nucleotide polymorphism (SNP)-chips to characterize genomic imbalances. Seventy-nine cases were of the germinal center B-cell like (GCB) type of DLBCL, 49 of the activated B-cell like (ABC) subtype and 20 were type 3 DLBCL. Twenty-four regions of recurrent genomic gains and 38 regions of recurrent genomic losses were identified over the whole cohort, with a median of 25 imbalances per case for ABC-DLBCL and 19 per case for GCB-DLBCL. Several recurrent copy number changes showed differential frequencies in the GCB- and ABC-DLBCL subgroups, including gains of HDAC7A predominantly in GCB-DLBCL (38% of cases) and losses of BACH2 and CASP8AP2 predominantly in ABC-DLBCL (35%), hinting at disparate pathogenetic mechanisms in these entities. Correlating gene expression and copy number revealed a strong gene dosage effect in all tumors, with 34% of probesets showing a concordant expression change in affected regions. Two new potential tumor suppressor genes emerging from the analysis, CASP3 and IL5RA, were sequenced in 10 and 16 candidate cases, respectively. However, no mutations were found, pointing to a potential haploinsufficiency effect of these genes, considering their reduced expression in cases with deletions. This work thus describes differences and similarities in the landscape of genomic aberrations in the DLBCL subgroups in a large collection of cases, confirming already known targets, but also discovering novel copy number changes with possible pathogenetic relevance.
Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis.
Sex, Age
View SamplesMYC translocations are the biologic hallmark of Burkitt lymphomas but also occur in other mature B-cell lymphomas. If accompanied by chromosomal breaks targeting the BCL2 and/or BCL6 oncogenes, these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas (DHLs); otherwise, the term single-hit lymphoma (SHL) is applied. In order to characterize the biologic features of these MYC+ lymphomas other than Burkitt lymphomas, we explored, after exclusion of molecular Burkitt lymphoma (mBL) as defined by gene expression profiling (GEP), the molecular, pathological and clinical aspects of 80 MYC translocation (MYC+) lymphomas (31 SHL, 26 BCL2+/MYC+, 14 BCL6+/MYC+, 6 BCL2+/BCL6+/MYC+ and 3 MYC+ lymphomas with unknown BCL6 status). Comparison of SHL and DHL revealed no difference in frequency of MYC partner (IG/non-IG), genomic complexity or MYC expression and no differences in GEP. DHL showed a more frequent GCB-like GEP and higher IGH and MYC mutation rates. GEP revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ DHL. BCL2+/MYC+ DHL showed a more frequent GCB-like GEP. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In contrast to mBL and lymphomas without MYC break, SHL and DHL patients had similar poor outcome. Our data suggest that after excluding mBL, MYC+ lymphomas could be biologically widely lumped without further need for subclassification.
Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.
Sex, Age, Specimen part
View SamplesThe spectrum of entities, the therapeutic strategy and the outcome of mature aggressive B-cell lymphomas (maB-NHL) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHL have been studied in detail, data on molecular profiling of pediatric maB-NHL are hitherto lacking. Our aim was to characterize pediatric maB-NHL on the molecular level and to evaluate whether a molecular diagnosis of pediatric maB-NHL reveals clinically relevant groups.
Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials.
Age
View SamplesBackground: Germinal center B-cell (GCB) lymphomas are common in children and adults. The prognosis strongly depends on age. Subgroups of GCB-lymphomas are characterized by chromosomal translocations affecting immunoglobulin (IG) loci leading to oncogene deregulation.
Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults.
Sex, Age
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