|
| Status |
Public on Jan 15, 2015 |
| Title |
Enhancer Sequence Variants and Transcription Factor Deregulation Synergize to Construct Pathogenic Regulatory Circuits in B Cell Lymphoma (array) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Most B cell lymphomas arise in the germinal center (GC), where humoral immune responses evolve from potentially oncogenic cycles of mutation, proliferation, and clonal selection. Although lymphoma gene expression diverges significantly from GC-B cells, underlying mechanisms that alter the activities of corresponding regulatory elements (REs) remain elusive. Here we define the complete pathogenic circuitry of human follicular lymphoma (FL), which activates or decommissions transcriptional circuits from normal GC-B cells and commandeers enhancers from other lineages. Moreover, independent sets of transcription factors, whose expression is deregulated in FL, target commandeered versus decommissioned REs. Our approach reveals two distinct subtypes of low-grade FL, whose pathogenic circuitries resemble GC-B or activated B cells. Remarkably, FL-altered enhancers also are enriched for sequence variants, including somatic mutations, which disrupt transcription factor binding and expression of circuit-linked genes. Thus, the pathogenic regulatory circuitry of FL reveals distinct genetic and epigenetic etiologies for GC-B transformation.
|
| |
|
| Overall design |
Gene expression analysis was performed for follicular lymphoma, pheriphal blood and germinal center B cells using Affymetrix Human Gene 1.0 ST and 2.0 ST arrays
|
| |
|
| Contributor(s) |
Oltz EM, Payton JE, Koues OI |
| Citation(s) |
25607463, 27183590 |
| |
| Submission date |
Sep 30, 2014 |
| Last update date |
Jan 25, 2019 |
| Contact name |
Jacqueline Payton |
| E-mail(s) |
jpayton@wustl.edu
|
| Organization name |
Washington University School of Medicine
|
| Department |
Pathology and Immunology
|
| Street address |
660 S. Euclid Ave
|
| City |
St. Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL10739 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [probe set (exon) version] |
| GPL19251 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [probe set (exon) version] |
|
| Samples (30)
|
|
| This SubSeries is part of SuperSeries: |
| GSE62246 |
Enhancer Sequence Variants and Transcription Factor Deregulation Synergize to Construct Pathogenic Regulatory Circuits in B Cell Lymphoma |
|
| Relations |
| BioProject |
PRJNA262666 |
Less...
More...