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Series GSE16121 Query DataSets for GSE16121
Status Public on May 16, 2009
Title Integrated genomics approach to detect allelic imbalances in multiple myeloma, SNP data
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide dosage effect on gene and microRNA expression

Multiple myeloma (MM) is characterized by marked genomic instability. Beyond structural rearrangements, a relevant role in its biology is represented by allelic imbalances leading to significant variations in ploidy status. To better elucidate the genomic complexity of MM, we analyzed a panel of 45 patients using combined FISH and microarray approaches. Using a self-developed procedure to infer exact local copy numbers for each sample, we identified a significant fraction of patients showing marked aneuploidy. A conventional clustering analysis showed that aneuploidy, chromosome 1 alterations, hyperdiploidy and recursive deletions at 1p and chromosomes 13, 14 and 22 were the main aberrations driving samples grouping. Then, we integrated mapping information with gene and microRNAs expression profiles: a multiclass analysis of the identified clusters showed a marked gene-dosage effect, particularly concerning 1q transcripts, also confirmed by correlating gene expression levels and local copy number alterations. A wide dosage effect affected also microRNAs, indicating that structural abnormalities in MM closely reflect in their expression imbalances. Finally, we identified several loci in which genes and microRNAs expression correlated with loss-of-heterozygosity occurrence. Our results provide insights into the composite network linking genome structure and gene/microRNA transcriptional features in MM.

Keywords: Integrated genomics approach based on SNP microarray and FISH procedures to detect allelic imbalances in multiple myeloma.
Overall design Pathological bone marrow specimens from 41 MM and four plasma cell leukemia (PCL) patients at diagnosis. 250 nanograms of genomic DNA was processed and, in accordance with the manufacturer's protocols, 40 micrograms of fragmented biotin-labelled DNA were hybridized on GeneChip Human Mapping 50K XbaI Arrays (Affymetrix Inc.). The arrays were scanned using the GeneChip Scanner 3000 7G. The images were acquired using Affymetrix GeneChip® Operating Software (GCOS version 1.4). Copy number values for individual SNPs were extracted and converted from CEL files into signal intensities using GTYPE 4.1 and Affymetrix Copy Number Analysis Tool (CNAT 4.0.1) softwares. Genomic Smoothing analysis was performed by using the smoothing window of 0 Mb, and inferred copy number states were derived from a Hidden Markov Model (HMM) based algorithm implemented in CNAT 4.0.1. Circular Binary Segmentation (Ohlsen et al., 2004) was applied using DNAcopy package for R Bioconductor on raw data. FBN procedure was finally applied to infer exact local copy number as described in the mentioned Reference.
Contributor(s) Luca A, Laura M, Sonia F, Marta L, Adrian A, Ivo K, Katia T, Donata V, Cristina B, Francesco B, Giorgio LD, Antonino N
Citation(s) 19396863
Submission date May 15, 2009
Last update date Dec 22, 2017
Contact name Luca Agnelli
Phone +390223903581
Organization name IRCCS Istituto Nazionale dei Tumori
Department Department of Advanced Diagnostics
Street address Venezian 1
ZIP/Postal code 20133
Country Italy
Platforms (1)
GPL2005 [Mapping50K_Xba240] Affymetrix Human Mapping 50K Xba240 SNP Array
Samples (45)
GSM403332 MM-015_GWP
GSM403333 MM-016_GWP
GSM403334 MM-030_GWP
This SubSeries is part of SuperSeries:
GSE16122 A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma
BioProject PRJNA122809

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
GSE16121_RAW.tar 630.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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