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GSE43290
Homo sapiens
51 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Correlate the gene expression profiles with the most relevant patterns of chromosome abnormalities (cytogenetic subgroups of meningiomas) and the gene expression profiles could help to explain the differences in clinical behaviour of meningiomas.
Publication Title
Gene expression profiles of meningiomas are associated with tumor cytogenetics and patient outcome.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Correlate the gene expression profiles with the most relevant patterns of chromosome abnormalities (cytogenetic subgroups of gliomas) and the histopathology.
Publication Title
Gene expression profiles of human glioblastomas are associated with both tumor cytogenetics and histopathology.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 99 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell (NPC) to a clonal PC and from an indolent clonal PC to a malignant PC, we performed gene expression profiling in 20 patients with MGUS, 33 with high-risk SMM and 41 with MM. The analysis showed that 126 genes were differentially expressed in MGUS, SMM and MM as compared to NPC. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules (snoRNA) and zinc finger proteins. GADD45A was the most significant up-regulated gene in clonal PC compared to NPC. Several proapoptotic genes (AKT1 and AKT2) were downregulated and antiapoptotic genes (APAF1 and BCL2L1) were upregulated in MM, both symptomatic and asymptomatic, compared to MGUS. Myc mediated apoptosis signaling is one of the top canonical pathways differentiating the asymptomatic and symptomatic myeloma. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation in the transition from MGUS to SMM and to MM. In conclusion, our data show that although MGUS, SMM and MM are not clearly distinguishable groups according to their GEP, several signaling pathways and genes were significant deregulated in the different steps of transformation process.
Publication Title
Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
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.
Publication Title
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple Myeloma (MM) remains incurable, and new drugs with novel mechanisms of action are still needed. In this report, we have analyzed the action of Zalypsis, an alkaloid analogous to certain natural marine compounds, in MM. Zalypsis turned out to be the most potent antimyeloma agent we have tested so far, with IC50s from picomolar to low nanomolar ranges. It also showed remarkable ex vivo potency in plasma cells from patients and in MM cells in vivo xenografted in mice. Besides the induction of apoptosis and cell cycle arrest, Zalypsis provoked DNA double-strand-breaks (DSB), evidenced by an increase in phospho-Histone-H2AX and phospho-CHK2, followed by a striking overexpression of p53 in p53-wild type cell lines. In addition, in those cell lines in which p53 was mutated, Zalypsis also provoked DSB and induced cell death, although higher concentrations were required. Immunohistochemical studies in tumours also demonstrated Histone-H2AX phosphorylation and p53 overexpression. Gene expression profile studies were concordant with these results, revealing an important deregulation of genes involved in DNA-damage response. The potent in vitro and in vivo antimyeloma activity of Zalypsis uncovers the high sensitivity of tumour plasma cells to DSB, and strongly supports the use of this compound in MM patients.
Publication Title
Zalypsis: a novel marine-derived compound with potent antimyeloma activity that reveals high sensitivity of malignant plasma cells to DNA double-strand breaks.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Cell line
View Samples- Mus musculus, Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Kinesin spindle protein (KSP) inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (Arry-520), a KSP inhibitor, has demonstrated activity in heavily pretreated multiple myeloma (MM) patients. The aim of this work was to investigate the activity of filanesib in combination with an IMiDs plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. Results: Filanesib showed in vitro and in vivo synergy with all IMiDs plus dexamethasone treatment, particularly with the pomalidomide combination (PDF). Importantly, the in vivo synergy observed in this combination was more evident in large, highly proliferative tumors, and it was shown to be mediated by impairment of mitosis transcriptional control, an increase in monopolar spindles, cell cycle arrest and the induction of apoptosis in cells in proliferative phases. In addition, PDF increased the activation of the proapoptotic protein Bax, which has been previously associated with sensitivity to filanesib, and could potentially be used as a predictive biomarker of response to this combination. Conclusions: Our results provide preclinical evidence for the potential benefit of the combination of filanesib with pomalidomide and dexamethasone and es-tablished the basis for a recently activated trial being conducted by the Spanish MM group investigating this combination in relapsed MM patients.
Publication Title
The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The mechanisms of resistance to the antibody-drug conjugate, T-DM1, were studied on clones derived from breast cancer cell line, BT474.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples