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Series GSE77536 Query DataSets for GSE77536
Status Public on Jan 31, 2017
Title Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse [DNA copy number]
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary Multiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from 17 MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA. Taken together, these results showed that genomic heterogeneity, both at the DNA and RNA level, is a hallmark of MM transition from diagnosis to relapse.
Please note that an a first step all analyses were carried out independently in each series, being the number of samples of 40 in methylation, 38 in SNP and 34 in expression series. In the next step, association studies were performed only in the overlapping samples, being 34 matching samples between expression and methylation and 32 samples between expression and SNP data.
 
Overall design Nineteen paired bone marrow samples were obtained at diagnosis and relapse (n = 38). A CD138 positive PC isolation using the AutoMACs automated separation system was carried out in all the BM samples. DNA was extracted from samples frozen in RLT-Plus buffer using commercially available kits (Allprep Kit, Qiagen, Valencia, CA) and hybridized following manufacturer’s protocol.
 
Contributor(s) Krzeminski P, Corchete LA, García JL, López-Corral L, Fermiñán E, García EM, Martín AA, Hernández-Rivas JM, García-Sanz R, San Miguel JF, Gutiérrez NC
Citation(s) 27811368
Submission date Feb 03, 2016
Last update date Feb 01, 2017
Contact name Norma C. Gutiérrez
E-mail(s) normagu@usal.es
Phone +34923291384
Organization name Centro de Investigación del Cáncer de Salamanca
Department Hematologia
Lab 12
Street address Campus Miguel de Unamuno
City Salamanca
State/province Salamanca
ZIP/Postal code 37007
Country Spain
 
Platforms (1)
GPL18637 [CytoScan750K_Array] Affymetrix CytoScan 750K Array
Samples (38)
GSM2054048 Multiple myeloma. Pair 1. Diagnosis. [DNA copy number]
GSM2054049 Multiple myeloma. Pair 1. Relapse. [DNA copy number]
GSM2054050 Multiple myeloma. Pair 2. Diagnosis. [DNA copy number]
This SubSeries is part of SuperSeries:
GSE77540 Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse
Relations
BioProject PRJNA310754

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
GSE77536_RAW.tar 1.6 Gb (http)(custom) TAR (of CEL, CYCHP)
GSE77536_weighted_Log2_Ratios.txt.gz 134.4 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data provided as supplementary file
Processed data are available on Series record
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