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SiRNA smart pool silencing of master regulators of Follicular Lymphoma transformation to DLBCL

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE66714 | GEO | 2015/11/11

SECONDARY ACCESSION(S): PRJNA277769

REPOSITORIES: GEO

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siRNA smart pool silencing of master regulators of Follicular Lymphoma transformation to DLBCL

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

Transcription profiling of follicular lymphoma to diffuse large cell lymphoma

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

cDNA microarray assay of lymph node biopsies diagnosed as lymphoma or as reactive tissue

Project description:Gene expression profiling of biopsied human lymph node (LN) tissue comparing each patient sample against mobilised peripheral blood stem cells (PBSC), the reference channel Evaluate whether gene expression microarray can diagnose lymph node biopsies as reactive or as one of three main types of lymphoma: classical Hodgkin’s lymphoma (cHL), diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL).

2012-11-28 | GSE23647 | GEO

LymphomaTransformation

2005-10-18 | E-GEOD-3458 | biostudies-arrayexpress

LymphomaTransformation

2005-10-18 | GSE3458 | GEO

cDNA microarray assay of lymph node biopsies diagnosed as lymphoma or as reactive tissue

2012-11-28 | E-GEOD-23647 | biostudies-arrayexpress

Array based comparative genomic hybridisation analysis of 1 Mb resolution of 21 follicular lymphomas (FL), 31 transformed diffuse large B-cells lymphomas (DLBCL), 29 de novo DLBCL (10 of GC and 19 non-GC related immunophenotype).

Project description:Follicular lymphoma (FL) is one of the most common types of indolent B-cell lymphoma in Western countries. FL commonly transforms to more aggressive diffuse large B-cell lymphoma (DLBCL) at reported frequencies between 15 - 60%. We have used microarray comparative genomic hybridisation (aCGH) at 1 Mb resolution to study copy number changes in paired tumor samples (primary FL and a subsequent tDLBCL) as well as de novo DLBCL cases to outline genetic mechanisms of transformation from follicular lymphoma to diffuse large B-cell lymphoma. Single hybridization per case. 21 FL, 31 transformed DLBCL, 29 de novo DLBCL (10 GC and 19 non-GC DLBCL). Tumor labelled with Cy5 and reference with Cy3. Mixture of 20 normal male or female genomic DNA was used in sex-mismatched hybridization.

2014-04-18 | E-GEOD-56884 | biostudies-arrayexpress

2014-04-18 | GSE56884 | GEO

Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma.

Project description:follicular lymphoma (FL), the most common indolent non-Hodgkin’s lymphoma, remains incurable. A well-recognized complication of FL is its transformation to a diffuse large B-cell lymphoma (DLBCL)-morphology in a subset of patients, for which the clinical outcomes are poor. Recent genetic profiling and single case studies of donor-derived FL following stem cell transplantation had alluded to the putative existence of a ‘long lived’ tumor-initiating progenitor cell compartment from which successive disease events occurred. To chronicle the genetic changes associated with progression to transformation, we conducted whole-genome sequencing (WGS) of FL-tFL pairs and matched germline (GL) samples from six patients, a total of 20 genomes.

| EGAS00001000399 | EGA

Gene expression data from serial samples of follicular lymphoma (FLSB - follicular lymphoma serial biopsies)

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

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