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Series GSE121912 Query DataSets for GSE121912
Status Public on Mar 13, 2019
Title Multiple myeloma immunoglobulin lambda translocations portend poor prognosis
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years. To better understand and identify these ‘high-risk’ cases, we analyzed the translocation landscape of myeloma from 795 newly-diagnosed patients by whole genome sequencing from the CoMMpass study. Translocations involving the immunoglobulin lambda (IgL) locus were identified in 10% of patients, and were indicative of poor prognosis. Importantly, 70% of IgL translocations co-occurred with hyperdiploid disease, a marker of standard risk, potentially resulting in the misclassification of IgL-translocated myeloma. Most IgL-translocations coincided with focal amplifications that were centered on the 3’ enhancer. Patients with IgL-translocations failed to benefit from immunomodulatory imide drugs (IMiDs), which target the lymphocyte-specific transcription factor IKZF1 that is bound to the IgL 3’ enhancer at some of the highest levels in the myeloma epigenome. These data implicate IgL-translocation as a driver of poor prognosis which may be due in part to IMID resistance.
Overall design Several myeloma cell lines were characterized for chromatin accessibility
Contributor(s) Barwick BG
Citation(s) 31015454, 33649772
Submission date Oct 29, 2018
Last update date Mar 12, 2021
Contact name Benjamin G Barwick
Phone (404) 285-2964
Organization name Emory University
Department Hematology and Medical Oncology
Lab Barwick Lab
Street address 1365 Clifton Rd. NE WCI-C 4th Floor Benches 36-37
City Atlanta
State/province GA
ZIP/Postal code 30322
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (28)
GSM3449815 H1112
GSM3449816 Karpas620-Ctrl
GSM3449817 Karpas620-Len
BioProject PRJNA499054
SRA SRP167124

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Supplementary file Size Download File type/resource
GSE121912_MACS2_q_0.01.union.annot.clean.bed.gz 1.5 Mb (ftp)(http) BED
GSE121912_MACS2_q_0.01.union.annot.clean.cts.txt.gz 11.6 Mb (ftp)(http) TXT
GSE121912_MACS2_q_0.01.union.annot.clean.det.txt.gz 2.0 Mb (ftp)(http) TXT
GSE121912_MACS2_q_0.01.union.annot.clean.rppm.cov.txt.gz 22.7 Mb (ftp)(http) TXT
GSE121912_RAW.tar 3.9 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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