Gene expression data from serial samples of follicular lymphoma (FLSB - follicular lymphoma serial biopsies)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE53820 | GEO | 2014/01/07
SECONDARY ACCESSION(S): PRJNA233454
REPOSITORIES: GEO
Similar Datasets
Project description:Transformation of follicular lymphoma (FL) to a more aggressive disease is associated with rapid progression and death. Existing molecular markers for transformation are few and their clinical impact is limited. Here, we report on a whole-genome study of DNA copy numbers and gene expression profiles in serial FL biopsies. We identified 698 genes with high correlation between gene expression and copy number and the molecular network most enriched for these cis-associated genes. This network includes 14 cis-associated genes directly related to the NFκB pathway. For each of these 14 genes, the correlated NFκB target genes were identified and corresponding expression scores defined. The scores for six of the cis-associated NFκB pathway genes (BTK, IGBP1, IRAK1, ROCK1, TMED7-TICAM2 and TRIM37) were significantly associated with transformation. The results suggest that genes regulating B-cell survival and activation are involved in transformation of FL Expression profiles were obtained from 81 biopsies origniating from 41 patients diagnosed with follicular lymphoma using Affymetrix HG U133 Plus 2.0 Gene Chip. Of these, 49 biopsies were from 24 patients with subsequent transformation to higher-grade lymphoma (DLBCL) (43 with histological diagnosis FL and 6 with DLBCL) and 32 biopsies were from 17 patients without any signs transformation
2014-01-07 | E-GEOD-53820 | biostudies-arrayexpress
Project description:Transformation of Follicular Lymphoma to Diffuse Large Cell Lymphoma: Alternative Patterns with Increased or Decreased Expression of c-myc and its Regulated genes The natural history of follicular lymphoma (FL) is frequently characterized by transformation to a more aggressive diffuse large B cell lymphoma (DLBCL). We compared the gene expression profiles between transformed DLBCL and their antecedent FL. No genes were observed to increase or decrease their expression in all the cases of histological transformation. However, two different gene expression profiles associated with the transformation process were defined, one in which c-myc and genes regulated by c-myc showed increased expression and one in which these same genes showed decreased expression. Further, there was a striking difference in gene expression profiles between transformed DLBCL and de novo DLBCL, since the gene expression profile of transformed DLBCL was more similar to their antecedent FL than to de novo DLBCL. The study demonstrates that transformation from FL to DLBCL can occur by alternative pathways and that transformed DLBCL and de novo DLBCL have very different gene expression profiles that may underlie the different clinical behaviors of these two types of morphologically similar lymphomas.
2005-09-23 | E-SMDB-963 | biostudies-arrayexpress
Project description:Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma involving germinal centre B cells, with a subset of patients undergoing transformation to a diffuse large B-cell lymphoma (DLBCL) morphology for which the clinical outcomes are poor. To elucidate the differences in copy number profiles between FL and tFL groups, we performed Affymetrix SNP 6.0 Array analysis on 31 paired FL-tFL cases. We wanted to identify and compare recurrent somatic copy number alterations (CNAs) between the two groups (FL vs. tFL). In addition, the concordance and discordance in the copy neutral loss of heterozygosity (cnLOH) between the two groups were also investigated to identify recurrent target gene regions.
2013-10-01 | GSE42525 | GEO
Project description:Follicular lymphoma (FL) is the most common indolent type of B-cell non-Hodgkin lymphoma. Advances in treatment have improved overall survival, but early relapse or transformation to aggressive disease is associated with inferior outcome. To identify early genetic events and track tumor clonal evolution, we performed multi-omics analysis of 94 longitudinal biopsies from 44 FL patients; 22 with transformation (tFL) and 22 with relapse without transformation (nFL). Deep whole-exome sequencing confirmed recurrent mutations in genes encoding epigenetic regulators (CREBBP, KMT2D, EZH2, EP300), with similar mutational landscape in nFL and tFL patients. Calculation of genomic distances between longitudinal samples revealed complex evolutionary patterns in both subgroups. CREBBP and KMT2D mutations were identified as genetic events that occur early in the disease course, and cases with CREBBP KAT domain mutations had low risk of transformation. Gains in chromosomes 12 and 18 (TCF4), and loss in 6q were identified as early and stable copy number alterations. Identification of such early and stable genetic events may provide opportunities for early disease detection and disease monitoring. Integrative analysis revealed that tumors with EZH2 mutations exhibited reduced gene expression of numerous histone genes, including histone linker genes. This might contribute to the epigenetic dysregulation in FL.
2024-08-20 | GSE272403 | GEO
Project description:Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma involving germinal centre B cells, with a subset of patients undergoing transformation to a diffuse large B-cell lymphoma (DLBCL) morphology for which the clinical outcomes are poor. To elucidate the differences in copy number profiles between FL and tFL groups, we performed Affymetrix SNP 6.0 Array analysis on 31 paired FL-tFL cases. We wanted to identify and compare recurrent somatic copy number alterations (CNAs) between the two groups (FL vs. tFL). In addition, the concordance and discordance in the copy neutral loss of heterozygosity (cnLOH) between the two groups were also investigated to identify recurrent target gene regions. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from follicular lymphoma (FL), transformed follicular lymphoma (tFL) and matching germline (GL) sample (if available). Copy number analysis of Affymetrix SNP 6.0 Array were performed on 91 DNA samples, consisting of 31 patients. Among the 31 patients, 19 had matching germline samples, while 12 had no germline samples. The Log R Ratio (LRR) values and the B Allele Frequency (BAF) values were subsequently calculated to search for copy number aberrations and copy neutral (CN)-LOH in the FL and tFL samples. Paired and unpaired analyses were performed accordingly.
2013-10-01 | E-GEOD-42525 | biostudies-arrayexpress
Project description:Follicular lymphoma (FL) is the most common indolent subtype of non-Hodgkin’s lymphoma, with relatively long overall survival rate ranging from 6 to 10 years from time of diagnosis. However, 20-60% of FL patients undergo transformation to aggressive diffuse large B cell lymphoma (DLBCL), with a reduced median survival of about 1.2 years. The specific functional and genetic determinants of FL transformation are still elusive and only a relatively small fraction of the cases is accounted for by established, recurrent alterations in TP53, MYC and BCL6, inactivation of CDKN2A and CDKN2B, or amplification of REL. We addressed this deficiency by performing systematic analysis of a B cell specific regulatory model with FL transformation signatures, using the Master Regulator Inference algorithm (MARINa). We show that the candidate master regulators inferred by the algorithm in FL induce synthetic lethality in DLBCL cells and lead to identification of specific compound combinations inducing synergistic loss of viability in transformed DLBCL cells
2015-11-11 | GSE66714 | GEO
Project description:The hallmark of follicular lymphoma (FL) is the t(14;18) chromosomal translocation. However, constitutive expression of anti-apoptotic Bcl-2 alone is insufficient for lymphomagenesis and subsequent molecular hits are required. We explored the role of microRNA (miRNA or miR) in the biology of FL by generating miRNA profiles of enriched sorted grade 1 and 2 FL tumor cells derived from 18 patients compared with enriched germinal center B-cells derived from seven follicular hyperplasia (FH). Expression levels of 851 human miRs were assayed and 133 miRs were significantly differentially expressed in FL tumor cells. The expression of 44 miRs in three major groups generated a unique FL signature. MiRs in group 1 were increased in FL (miR-193-5p, -193b*, -345, -513b, -574-3p, -584, -663, -1287, -1295, and -1471). Group 2 was increased in the majority of FL cases but showed lower levels of expression in a subset of FL (let-7a, let-7f, miR-7-1*, -9, -9*, -20a, -20b, -30b, -96, -98, -194, -195, -221*, -374a, -451, -454, -502-3p, -532-3p, -574-3p, -664*, -1274a, -1274b, and -1260). MiR group 3 was decreased in FL (miR-17*, -30a, 33a, 106a*, -141, 202, -205, -222, 301b, -431*, and -570). Two patterns within FL were detected, largely due to the variable expression of group 2 miRs. The pattern with higher expression of group 2 miRs was associated with complete response to chemotherapy. Gene expression analysis of 199 genes related to lymphoma and tumor development performed in tandem indicated differential expression of 47 genes in FL including increased expression of AKT-1, PRKCE, IL4R, DROSHA, and MAPK1; and decreased expression of CHEK1, RAD51, CDKN1A, SOCS2, KLF4, BLIMP1 and IRF4. Functional studies provide evidence that miR-20a and -20b target CDKN1A/p21, miR-194 targets SOCS2, and miR-301b targets MAPK1 in FL, affecting cell proliferation and potentially contributing to lymphomagenesis. These findings suggest a role for aberrant miRNA expression in the biology of FL with prognostic and mechanistic implications.
2012-05-03 | GSE28090 | GEO
Project description:We studied 277 lymphoma samples (198 FL and 79 transformed FL [tFL]) using a single-nucleotide polymorphism array to identify the secondary chromosomal abnormalities that drive the development of FL and its transformation to diffuse large B-cell lymphoma.
2015-03-30 | GSE67385 | GEO
Project description:Follicular lymphoma (FL) is the most common indolent subtype of non-Hodgkinâs lymphoma, with relatively long overall survival rate ranging from 6 to 10 years from time of diagnosis. However, 20-60% of FL patients undergo transformation to aggressive diffuse large B cell lymphoma (DLBCL), with a reduced median survival of about 1.2 years. The specific functional and genetic determinants of FL transformation are still elusive and only a relatively small fraction of the cases is accounted for by established, recurrent alterations in TP53, MYC and BCL6, inactivation of CDKN2A and CDKN2B, or amplification of REL. We addressed this deficiency by performing systematic analysis of a B cell specific regulatory model with FL transformation signatures, using the Master Regulator Inference algorithm (MARINa). We show that the candidate master regulators inferred by the algorithm in FL induce synthetic lethality in DLBCL cells and lead to identification of specific compound combinations inducing synergistic loss of viability in transformed DLBCL cells RNA was obtained from 45 samples, which included siRNA silencing of 5 single transcription factors, 5 combinations of two transcription factors and non-target control in triplicates.
2015-11-11 | E-GEOD-66714 | biostudies-arrayexpress
Project description:The hallmark of follicular lymphoma (FL) is the t(14;18) chromosomal translocation. However, constitutive expression of anti-apoptotic Bcl-2 alone is insufficient for lymphomagenesis and subsequent molecular hits are required. We explored the role of microRNA (miRNA or miR) in the biology of FL by generating miRNA profiles of enriched sorted grade 1 and 2 FL tumor cells derived from 18 patients compared with enriched germinal center B-cells derived from seven follicular hyperplasia (FH). Expression levels of 851 human miRs were assayed and 133 miRs were significantly differentially expressed in FL tumor cells. The expression of 44 miRs in three major groups generated a unique FL signature. MiRs in group 1 were increased in FL (miR-193-5p, -193b*, -345, -513b, -574-3p, -584, -663, -1287, -1295, and -1471). Group 2 was increased in the majority of FL cases but showed lower levels of expression in a subset of FL (let-7a, let-7f, miR-7-1*, -9, -9*, -20a, -20b, -30b, -96, -98, -194, -195, -221*, -374a, -451, -454, -502-3p, -532-3p, -574-3p, -664*, -1274a, -1274b, and -1260). MiR group 3 was decreased in FL (miR-17*, -30a, 33a, 106a*, -141, 202, -205, -222, 301b, -431*, and -570). Two patterns within FL were detected, largely due to the variable expression of group 2 miRs. The pattern with higher expression of group 2 miRs was associated with complete response to chemotherapy. Gene expression analysis of 199 genes related to lymphoma and tumor development performed in tandem indicated differential expression of 47 genes in FL including increased expression of AKT-1, PRKCE, IL4R, DROSHA, and MAPK1; and decreased expression of CHEK1, RAD51, CDKN1A, SOCS2, KLF4, BLIMP1 and IRF4. Functional studies provide evidence that miR-20a and -20b target CDKN1A/p21, miR-194 targets SOCS2, and miR-301b targets MAPK1 in FL, affecting cell proliferation and potentially contributing to lymphomagenesis. These findings suggest a role for aberrant miRNA expression in the biology of FL with prognostic and mechanistic implications. miRNA profiling was performed using Agilent miRNA array platform with RNAs isolated from sorted follicular lymphoma B cells and follicular hyperplasia B cells.
2012-05-02 | E-GEOD-28090 | biostudies-arrayexpress