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GSE22170
Mus musculus
20 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of the expression profile of adult mice heterozygous for Pitx2 isoform C.
Publication Title
PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibility and complex changes in gene expression.
Sample Metadata Fields
Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 19 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The SCH9 null strain has smaller cell size, grows at a slower rate and survives three times longer than wide-type yeast.
Publication Title
Comparative analyses of time-course gene expression profiles of the long-lived sch9Delta mutant.
Sample Metadata Fields
Age
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The three yeast mutants sch9, ras2, tor1 show extended chronological life span up to three folds.
Publication Title
Significant and systematic expression differentiation in long-lived yeast strains.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 102 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Karyotypic instability, including numerical and structural chromosomal aberrations, represents a distinct feature of multiple myeloma (MM). 40-50% of patients displayed hyperdiploidy, defined by recurrent trisomies of non-random chromosomes. To characterize hyperdiploid (H) and nonhyperdiploid (NH) MM molecularly, we analyzed the gene expression profiles of 66 primary tumors, and used FISH to investigate the major chromosomal alterations. The differential expression of 225 genes mainly involved in protein biosynthesis, transcriptional machinery and oxidative phosphorylation distinguished the 28 H-MM from the 38 NH-MM cases. The 204 upregulated genes in H-MM mapped mainly to the chromosomes involved in hyperdiploidy, and the29% up-regulated genes in NH-MM mapped to 16q. The identified transcriptional fingerprint was robustly validated on a publicly available gene expression dataset of 64 MM cases; and the global expression modulation of regions on the chromosomes involved in hyperdiploidy was verified using a self-developed non-parametric statistical method. We showed that H-MM could be further divided into two distinct molecular and transcriptional entities, characterized by the presence of trisomy 11 and 1q-extracopies/chromosome 13 deletion, respectively. Our data reinforce the importance of combining molecular cytogenetics and gene expression profiling to define a genomic framework for the study of MM pathogenesis and clinical management.
Publication Title
Upregulation of translational machinery and distinct genetic subgroups characterise hyperdiploidy in multiple myeloma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 158 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Mapping 50K Xba240 SNP Array (mapping50kxba240)
Description
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
Publication Title
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 158 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
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.
Publication Title
A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide gene dosage effect.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 90 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background and objective: The chromosome 13 deletion (del(13)) represents one of the most frequent chromosomal alterations in multiple myeloma (MM). del(13) is associated with an unfavorable prognosis, although there is an increasing agreement that its prognostic relevance has to be related to the ploidy status and the presence of different chromosomal translocations. This study is aimed at providing a comprehensive analysis of the transcriptional features of del(13) in MM. Design and methods: Highly purified plasma cells from 80 newly diagnosed MM patients were characterized by means of FISH and high-density oligonucleotide microarray for gene expression profiling and chromosomal alterations. Results: We identified 67 differentially expressed genes in the del(13)+ and del(13)- groups, all of which downregulated in the del(13)+ cases: 44 mapped along the whole chromosome 13, seven on chromosome 11 and three on chromosome 19. Functional analyses of the selected genes indicated their involvement in protein biosynthesis, ubiquitination and transcriptional regulation. An integrative genomic approach based on regional analyses of the gene expression data identified distinct chromosomal regions whose global expression modulation could differentiate del(13)+, in particular the upregulation of 1q21-1q42 and the downregulation of 19p and almost the entire chromosome 11. FISH analyses confirmed the close relationship between del(13)+ and the presence of extracopies of 1q21-1q42 (P=6x10-4) or the absence of chromosome 11 and 19 trisomy (P=5x10-4). Interpretation and conclusions: Our results indicate that distinct types of chromosomal aberrations are closely related to the transcriptional profiles of del(13)+, suggesting that the contribution of del(13) on the malignancy should be considered together with associated abnormalities.
Publication Title
Integrative genomic analysis reveals distinct transcriptional and genetic features associated with chromosome 13 deletion in multiple myeloma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may play a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM), by profiling puri?ed malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCL) and 4 normal controls. Overall, a global sno/scaRNAs down-regulation was found in MMs and at more extent in sPCLs compared to normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the TC4 MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by imprinting mechanism at 15q11. However, the imprinting center resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information into the bio-molecular complexity of plasma cell dyscrasias.
Publication Title
The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In order to investigate the patterns of genetic lesions in a panel of 23 Human Multiple Myeloma Cell Lines (HMCLs), we made a genomic integrative analysis involving FISH and both gene expression and genome-wide profiling approaches. The expression profiles of the genes targeted by the main IGH translocations showed that the WHSC1/MMSET gene involved in t(4;14)(p16;q32) was expressed at different levels in all of the HMCLs, and that the expression of the MAF gene was not restricted to the HMCLs carrying t(14;16)(q32;q23). Supervised analyses identified a limited number of genes specifically associated with t(4;14) and involved in different biological processes. The signature related to MAF/MAFB expression included the known MAF target genes CCND2 and ITGB7, as well as genes controlling cell shape and cell adhesion. Genomewide DNA profiling allowed the identification of a gain on chromosome arm 1q in 88% of the analyzed cell lines, together with recurrent gains on 8q, 18q, 7q and 20q; the most frequent deletions affected 1p, 13q, 17p and 14q; and almost all of the cell lines presented LOH on chromosome 13. Two hundred and twenty-two genes were found to be simultaneously overexpressed and amplified in our panel, including the BCL2 locus at 18q21.33. Our data further support the evidence of the genomic complexity of multiple myeloma and reinforce the role of an integrated genomic approach in improving our understanding of the molecular pathogenesis of the disease.
Publication Title
Molecular characterization of human multiple myeloma cell lines by integrative genomics: insights into the biology of the disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Conditional expression of dominant-negative HIF1a in zebrafish cardiomyocytes severely inhibits heart regeneration. To understand more about the mechanism, we performed microarray analysis of wildtype regenerating zebrafish and dnHIF1a regenerating zebrafish to determine which genes are regulated by hypoxia/HIF1a.
Publication Title
Hypoxia induces myocardial regeneration in zebrafish.
Sample Metadata Fields
Specimen part, Treatment
View Samples