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Series GSE145846 Query DataSets for GSE145846
Status Public on Sep 02, 2021
Title Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers (SNP array)
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary Dynamic changes to the epigenome are essential regulators of B cell differentiation and, when perturbed, can lead to cancer. We compared three types of mature B cell lymphoma/leukemia (BCL) and normal lymphocytes to identify common and distinct epigenetic perturbations that promote oncogenesis. Purified malignant B cells from 52 patients (18 Follicular, 11 Diffuse Large B Cell, 23 Chronic Lymphocytic Lymphomas) and normal B cell subsets from 28 donor tonsils were subjected to chromatin immunoprecipitation and sequencing (ChIP-seq) for H3K4me1, H3K9/14ac, and H3K27ac; FAIRE-seq for open chromatin; RNA-seq; and genome copy number arrays. We identified a novel super enhancer (SE) connected to the aberrant expression of FCMR and PIGR in multiple BCL subtypes, which may drive the tissue-specific expression of the two immunoglobulin receptor genes. These integrative studies also revealed that loss of normal B cell SEs in BCL was associated with significant reduction in linked gene expression, the greatest impact among regulatory elements. Downregulation of crucial B cell transcription factors (TF) and tumor suppressors was consistent across BCL subtypes and linked to significantly diminished or absent active chromatin marks in adjacent SEs. These BCL-repressed SEs are enriched in binding sites for the same suppressed TFs that they regulate, suggesting transcriptional regulatory feedback loops for these key B cell identity genes. In sum, this study defined common alterations in the regulomes of mature B cell leukemias and lymphomas and implicate SEs as important hubs of tumor suppressing transcriptional feedback loops that are perturbed in B cell cancer.
Overall design Affymetrix Genome_Wide SNP6 arrays were performed according to the manufacturer's directions on DNA extracted from sorted B cells isolated from healthy tonsils, lymph nodes of follicular lymphoma or diffuse large B cell lymphoma patients, and peripheral blood of chronic lymphocytic leukemia patients.
Contributor(s) Andrews JM, Payton JE
Citation(s) 34461601
Submission date Feb 24, 2020
Last update date Dec 02, 2021
Contact name Jared Andrews
Organization name St. Jude Children's Research Hospital
Department Developmental Neurobiology
Street address 262 Danny Thomas Pl
City Memphis
State/province Tennessee
ZIP/Postal code 38105
Country USA
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (41)
GSM4337621 CLL140_snp
GSM4337622 CLL144_snp
GSM4337623 CLL158_snp
This SubSeries is part of SuperSeries:
GSE145848 Key Super Enhancers Drive Tumor-Suppressing Transcription Feedback Programs in Mature B Cell Cancers
BioProject PRJNA608515

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource 306.4 Mb (ftp)(http) TXT
GSE145846_RAW.tar 1.7 Gb (http)(custom) TAR (of CEL, CHP)
Processed data provided as supplementary file
Processed data are available on Series record

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