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Series GSE43272 Query DataSets for GSE43272
Status Public on Jan 04, 2013
Title MCL1 is deregulated in subgroups of diffuse large B-cell lymphoma
Organism Homo sapiens
Experiment type Genome variation profiling by genome tiling array
Summary MCL1 is an anti-apoptotic member of the BCL2 family that is deregulated in various solid and hematological malignancies. However, its role in the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL) is unclear. We analyzed gene expression profiling data from 350 DLBCL patient samples and detected that activated B-cell-like (ABC) DLBCLs express MCL1 at significantly higher levels compared to germinal center B-cell-like (GCB) DLBCL patient samples (p=2.7 x 10(-10)) [PMID 23257783]. Immunohistochemistry confirmed high MCL1 protein expression predominantly in ABC DLBCL in an independent patient cohort (n=249; p=0.001).
To elucidate molecular mechanisms leading to aberrant MCL1 expression, we analyzed array comparative genomic hybridization (aCGH) data of 203 DLBCL samples [GSE11318] and identified recurrent chromosomal gains/amplifications of the MCL1 locus that occurred in 26% of ABC DLBCLs. In addition, aberrant STAT3 signaling contributed to high MCL1 expression in this subtype. Knockdown of MCL1 as well as treatment with the BH3-mimetic obatoclax induced apoptotic cell death in MCL1 positive DLBCL cell lines. In summary, MCL1 is deregulated in a significant fraction of ABC DLBCLs and contributes to therapy resistance. These data suggest that specific inhibition of MCL1 might be utilized therapeutically in a subset of DLBCLs.
 
Overall design This GEO dataset is comprised of aCGH measurements for DLBCL cell lines, which are used in the above-mentioned paper. Cell lines were measured against the DNA of a healthy male donor who in turn was measured against a pool of healthy DNAs to correct for individual CNVs of the donor.
 
Contributor(s) Lenz G
Citation(s) 23257783
Submission date Jan 03, 2013
Last update date Oct 26, 2013
Contact name Michael Grau
Organization name University of Münster
Department Faculty of Medicine
Lab Translational Oncology
Street address Albert-Schweitzer-Campus 1
City Münster
State/province Nordrhein-Westfalen
ZIP/Postal code 48149
Country Germany
 
Platforms (1)
GPL15436 NimbleGen Human CGH 3x720K Whole-Genome Tiling v3.0 Array [090527_HG18_WG_CGH_v3.1_HX3]
Samples (13)
GSM1059798 DNA pool versus male control DNA, 2 replicates
GSM1059799 DLBCL cell line OCI-Ly03 versus male control DNA
GSM1059800 DLBCL cell line OCI-Ly10 versus male control DNA
Relations
BioProject PRJNA185203

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
GSE43272_RAW.tar 401.6 Mb (http)(custom) TAR (of PAIR)
GSE43272_full_normalized_data.txt.gz 52.7 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record

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