Genome-wide analysis of t(14;18)-negative/BCL2 expression-negative FL
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE80103 | GEO | 2020/11/23
REPOSITORIES: GEO
Similar Datasets
Project description:Pediatric-type follicular lymphoma (PTFL) is a variant of FL with distinctive clinico-pathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are not known.
2016-09-21 | GSE78872 | GEO
Project description:Background: 15% of high and 50% of low stage FL lack the t(14;18). Nevertheless, most of these cases express BCL2 by so far unknown mechanisms. Principals/Methodology: To find molecular mechanisms, triggering FL-pathogenesis in t(14;18)-negative FL, the exonic SNV-profiles of 33 FL with and 16 FL without t(14;18) were assessed by whole exome-sequencing and external SNV-data integration. The SNV-profile of the whole exome-sequenced FL was correlated with copy number, LOH and gene-expression data. Finally, the N-glycosylation status was assessed (LympTrack assay) in a separate validation cohort. Results: SNVs in FL with and without t(14;18) affected different genes, but accumulated in similar pathways, e.g. apoptosis, epigenetic processes and cell cycle/proliferation. Mutations in genes associated with immune-response were more prominently and those associated with NFkB and N-glycosylation selectively enriched in t(14;18)-negative FL. ~50% of mutated genes showed BCL2-asociation at high confidence in FL with and without t(14;18). Moreover, among the genes mutated in t(14;18)-negative FL 555 (~1/3) were affected by copy number alterations and/or copy-neutral LOH, 125 were differently expressed between FL with and without t(14;18) (p<0.01) and 62 were differentially expressed and affected by copy number alterations and/or copy-neutral LOH. N-glycosylation was strongly reduced in t(14;18)-negative FL as compared to results reported for historical FL cohorts. Conclusion: These results suggest a stronger crosstalk with the microenvironment that may compensate for the lack of N-glycosylation and a diverse portfolio of SNVs that may contribute to the upregulation of BCL2 and FL pathogenesis in t(14;18)-negative FL.
| EGAS00001002164 | EGA
Project description:Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFƒÛB, proliferation and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FL, in which 32% of t(14;18)-negative FL showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.
2009-06-03 | GSE16131 | GEO
Project description:Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied regarding their immunohistochemical, genetic, molecular and clinical features. Within a previously published series of 184 FL grade 1-3A with available gene expression data, we identified 17 FL lacking the t(14;18). Comparative genomic hybridization and high resolution SNP array profiling demonstrated that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles revealed an enrichment of germinal center B-cell associated signatures in t(14;18)-positive FL, whereas activated B-cell like, NFƒÛB, proliferation and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FL, in which 32% of t(14;18)-negative FL showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL. Fresh-frozen tumor-biopsy specimens were obtained from 184 untreated patients who had received a diagnosis of follicular lymphoma. RNA was extracted from the biopsy specimens and was examined for gene expression with the use of Affymetrix U133A and U133B microarrays.
2009-06-02 | E-GEOD-16131 | biostudies-arrayexpress
Project description:Genome-wide analysis of t(14;18)-negative/BCL2 expression-negative FL
| PRJNA317923 | ENA
Project description:MALT lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the NF-κB pathway. Gastric MALT lymphomas harboring such translocation do not respond to H. pylori eradication, while those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 24 MALT lymphomas (15 translocation-positive, 9 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-κB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions showed that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-κB target genes, particularly TLR6, CCR2, CD69 and BCL2, while translocation-negative cases were featured by active inflammatory and immune responses, such as IL8, CD86, CD28 and ICOS. Separate analyses of the genes differentially expressed between translocation-positive and negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10 mediated NF-κB activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors. This study compares MALT with other lymphomas, namely follicular lymphomas (FL) and mantle cell lymphomas (MCL), and investigates the molecular mechanisms of the lymphomagenesis between translocation-positive versus -negative MALT lymphoma cases in order to derive the pathways leading to MALT lymphoma pathogenesis. The study uses fresh frozen tissues from 24 MALT lymphoma cases with 7 FL and 7 MCL. Samples were run on the HG-U133A, HG-U133B, and HG-U133 plus2 GeneChips.
2010-10-07 | E-GEOD-16024 | biostudies-arrayexpress
Project description:Follicular lymphoma (FL) is an indolent, but incurable subtype of non-Hodgkin lymphoma. These tumor harbor t (14;18) translocation in at least 90% of patients. Recently, activating EZH2 mutations have been Follicular lymphoma (FL) is an indolent, but incurable subtype of non-Hodgkin lymphoma. These tumor harbor t (14;18) translocation in at least 90% of patients. Recently, activating EZH2 mutations have been found in a significant number of patients with FL. Gene expression profiling (GEP) was performed to determine differential gene-expression between the EZH2 mutated vs unmutated subgroups in FL.
2014-07-01 | GSE55267 | GEO
Project description:GCB subtype DLBCL with BCL2 translocation
| PRJNA744546 | ENA
Project description:RNA-seq data for 6 de novo GCB subtype DLBCL patients with BCL2 translocation
2022-07-01 | GSE179689 | GEO
Project description:Follicular lymphoma (FL) is an indolent, but incurable subtype of non-Hodgkin lymphoma. These tumor harbor t (14;18) translocation in at least 90% of patients. Recently, activating EZH2 mutations have been Follicular lymphoma (FL) is an indolent, but incurable subtype of non-Hodgkin lymphoma. These tumor harbor t (14;18) translocation in at least 90% of patients. Recently, activating EZH2 mutations have been found in a significant number of patients with FL. Gene expression profiling (GEP) was performed to determine differential gene-expression between the EZH2 mutated vs unmutated subgroups in FL. Total RNA extracted from fresh frozen specimens with FL diagnosis were processed for hybridization to Affymetrix HG-U133 plus 2 arrays. To enhance the identification of differential gene expression in FL tumor cells only, FL cases with a high B-cell content (enriched B-cell signature of >2-fold above the mean of the B-cell signature (pan B-cell markers) in the entire FL data set) were chosen for analysis.
2014-07-01 | E-GEOD-55267 | biostudies-arrayexpress