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Series GSE8388 Query DataSets for GSE8388
Status Public on Nov 01, 2007
Title Epigenetic upregulation of B-cell inappropriate genes induces extinction of B-cell program in classical Hodgkin lymphoma
Organism Homo sapiens
Experiment type Expression profiling by array
Summary A unique feature of the tumour cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events, especially promoter DNA-methylation, are involved in this silencing of many B-cell associated genes. Here we show that DNA-demethylation alone or in conjunction with histone-acetylation is not able to reconstitute the B-cell gene expression program in cultured HRS cells. Instead, combined DNA-demethylation and histone-acetylation of B cells induce a nearly complete extinction of their B-cell expression program and a tremendous up-regulation of numerous cHL characteristic genes including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the up-regulation of cHL characteristic genes and the extinction of the B-cell expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic up-regulation of cHL characteristic genes thus play - in addition to promoter DNA-hypermethylation of B-cell associated genes – a pivotal role for the reprogramming of HRS cells and explain why DNA-demethylation alone is unable to reconstitute the B-cell expression program in HRS cells.
Keywords: Epigenetic modification
Overall design 5-aza-dC treatment:
The cHL derived cell lines L428, KMH2 and L1236 were treated with 5-aza-dC at a concentration of 5 µM for 5 days with drug and medium replacement after each 48 hours.

Combined 5-aza-dC/TSA treatment:
The Burkitt lymphoma derived cell lines (Daudi, Namalwa and Raji)were treated with 5-aza-dC at a concentration of 3 µM for 6 days. 5-aza-dC and medium was replaced at day 2 and 5. At the fifth day - in addition to 3 µM 5-aza-dC - cells were incubated for 24 hours with 625 nM TSA.

The gene expression profiles of the untreated and treated cell lines were generated in duplicates.
Contributor(s) Ehlers A, Oker E, Bentink S, Lenze D, Stein H, Hummel M
Citation(s) 18256685
Submission date Jul 05, 2007
Last update date Aug 10, 2018
Contact name Anke Ehlers
Organization name Charité Universitätsmedizin
Department Institute of Pathology
Street address Hindenburgdamm 30
City Berlin
State/province Berlin
ZIP/Postal code 12200
Country Germany
Platforms (1)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
Samples (24)
GSM207568 Daudi + 5 µM 5-aza-dC (6 days) + 625 nM TSA (24 h) (1)
GSM207577 Daudi + 5 µM 5-aza-dC (6 days) + 625 nM TSA (24 h) (2)
GSM207578 Daudi untreated (1)
BioProject PRJNA101427

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Supplementary file Size Download File type/resource
GSE8388_RAW.tar 223.0 Mb (http)(custom) TAR (of CEL, CHP, EXP)
Processed data included within Sample table
Processed data provided as supplementary file

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