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GSE46261
Homo sapiens
228 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs are non-coding RNAs involved in the maturation of other RNA molecules. Alterations of sno/scaRNA expression may play a role in cancerogenesis. This study elucidates the patterns of sno/scaRNA expression in highly purified cells from 211 chronic lymphocytic leukemia (CLL) patients (Binet stage A) also in comparison with those of different normal B-cell subsets. CLLs display a sno/scaRNAs expression profile similar to normal memory, nave and marginal-zone B-cells, with the exception of a few down-regulated transcripts (SNORA31, -6, -62, and -71C). Our analyses also suggest some heterogeneity in the pattern of sno/scaRNAs expression which is apparently unrelated to the major biological (ZAP-70 and CD38), molecular (IGHV mutation) and cytogenetic markers. Moreover, we found that SNORA70F was significantly down-regulated in poor prognostic subgroups and this phenomenon was associated with the down-regulation of its host gene COBLL1. Finally, we generated an independent model based on SNORA74A and SNORD116-18 expression, which appears to distinguish two different prognostic CLL groups. These data extend the view of sno/scaRNAs deregulation in cancer and may contribute to discover novel biomarkers associated with the disease and potentially useful to predict the clinical outcome of early stage CLL patients.
Publication Title
Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course that reflects its heterogeneous genomic pattern. To better define molecular subtypes of the disease, we performed SNP and gene expression profiling microarray analyses in a panel of early stage (Binet A) patients. A clustering analysis of genomic profiles identified four significant groups mainly driven by del(13)(q14) and trisomy 12. Notably, patients with del(13)(q14) were grouped in two separate clusters based on the presence of a biallelic loss and the extension of the deletion. The shorter monoallelic deleted 13q14 region was found to be 635 kb in length, not encompassing the mir-15a/16-1 locus. Interestingly, the mir-15a and mir-16 expression was found to be significantly down-regulated only in patients with biallelic loss. Furthermore, a multiclass supervised analysis identified a different transcriptional signatures in the two genomic subgroups with del(13)(q14). Finally, an integrative approach identified 93 transcripts, mainly mapped to chromosome 12 and 13q12-q14.3, whose expression was significantly correlated with the DNA copy number. Overall, our data further support the notion that transcription deregulation in B-CLL could be mostly due to a gene dosage effect and underscore the presence of two distinct molecular types of 13q14 deleted patients with potential clinical relevance.
Publication Title
Integrative genomics analyses reveal molecularly distinct subgroups of B-cell chronic lymphocytic leukemia patients with 13q14 deletion.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Distinct genetic abnormalities such as TP53 deletion at 17p13.1, have been identified as having an adverse prognostic relevance in B-cell chronic lymphocytic leukemia (B-CLL). Conventional cytogenetic studies have shown that TP53 deletion in B-CLL is associated predominantly with 17p loss resulting from complex chromosomal rearrangements. We performed genome-wide DNA (SNPs arrays), fluorescence in situ hybridization (FISH) and gene expression profiling (GEP) analyses to investigate the significance of 17p loss in a panel of 71 genetically well-characterized B-CLLs in Binet stage A, 18 of which carried a TP53 monoallelic deletion. Combined SNP arrays and FISH approaches showed 17p loss in all of the TP53-deleted cases, with breakpoints scattered along the 17p11.2 region. Mutations in exons 5 to 9 of TP53 were found in 9/12 deleted samples. GEP of 60 B-CLLs, including 7 patients with 17p loss, identified 40 differentially expressed genes in 17p- versus 17p normal samples, 35 of which were down-regulated in 17p- tumors. The majority (30/35) of these transcripts, including putative tumor suppressor genes, mapped to 17p. Overall, these data indicate that, beside TP53 deletion, the concomitant loss of 17p arm may contribute to the strong negative prognostic impact known to be associated with this lesion in B-CLL.
Publication Title
Molecular and transcriptional characterization of 17p loss in B-cell chronic lymphocytic leukemia.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 60 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Distinct genetic abnormalities such as TP53 deletion at 17p13.1, have been identified as having an adverse prognostic relevance in B-cell chronic lymphocytic leukemia (B-CLL). Conventional cytogenetic studies have shown that TP53 deletion in B-CLL is associated predominantly with 17p loss resulting from complex chromosomal rearrangements. We performed genome-wide DNA (SNPs arrays), fluorescence in situ hybridization (FISH) and gene expression profiling (GEP) analyses to investigate the significance of 17p loss in a panel of 71 genetically well-characterized B-CLLs in Binet stage A, 18 of which carried a TP53 monoallelic deletion. Combined SNP arrays and FISH approaches showed 17p loss in all of the TP53-deleted cases, with breakpoints scattered along the 17p11.2 region. Mutations in exons 5 to 9 of TP53 were found in 9/12 deleted samples. GEP of 60 B-CLLs, including 7 patients with 17p loss, identified 40 differentially expressed genes in 17p- versus 17p normal samples, 35 of which were down-regulated in 17p- tumors. The majority (30/35) of these transcripts, including putative tumor suppressor genes, mapped to 17p. Overall, these data indicate that, beside TP53 deletion, the concomitant loss of 17p arm may contribute to the strong negative prognostic impact known to be associated with this lesion in B-CLL.
Publication Title
Molecular and transcriptional characterization of 17p loss in B-cell chronic lymphocytic leukemia.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 2 Downloadable Samples
NextSeq 500
Description
We report the single-cell RNA sequencing data obtained from MDA-MB-231 breast cancer cells cultured in standard DMEM with 25 mM glucose, or adapted to culture in DMEM with 10 mM fructose to reduce glycolysis, and then cultured as mammospheres Overall design: Examination of transcriptomic changes in MDA-MB-231 breast cancer cells mammospheres in response to restriction of glycolysis
Publication Title
The effects of restricted glycolysis on stem-cell like characteristics of breast cancer cells.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 188 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 188 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Highly homologous B-cell receptors, stereotyped BCR, are expressed in a recurrent fraction of patients with chronic lymphocytic leukemia (CLL). In this study, we investigated the biological and molecular features of leukemic cells from 16 patients utilizing stereotyped subset #4 BCR (IGHV4-34) in a prospective cohort of 462 Binet stage A CLL patients. All subset #4 patients were characterized by the IGHV mutated gene configuration and by the absence of unfavorable cytogenetic lesions, and NOTCH1 and SF3B1 mutations. Gene expression profiling demonstrated a significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC genes in leukemic cells from subset #4 compared to those from the remaining IGHV-mutated patients. Similarly, in the cells from subset #4 cases there was a specific miRNA expression pattern involving the upregulation of miR-497 and miR-29c. Furthermore transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, known to be a validated target of this miRNA. Our data identify a distinct gene and miRNA expression profile of the cells from subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the leukemic cells.
Publication Title
Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Prospective series of 136 clinical monoclonal B lymphocytosis (cMBL) and 216 chronic lymphocytic leukemia (CLL) Rai 0 patients, were investigated in this study. While the distribution of CD38 and ZAP-70 positivity was similar, IGHV-mutated cases were more frequent among cMBL (P = 0.005). A Cox multivariate analysis on the whole patient cohort showed that cMBL condition was predictive of longer PFS, while CD38 expression and IGHV-unmutated status and CD38 expression correlated significantly with a shorter PFS in cMBL and Rai0-CLL, respectively. Trisomy 12, 11q- and 17p- abnormalities were scanty and of no predictive value in both conditions. Notably, gene and miRNA expression profiling showed no significant differences between cMBL and Rai0-CLL. Furthermore, similar gene and miRNA expression signatures were found in cMBL and Rai0-CLL according to the IGHV gene mutational status: that is, unmutated cases had different signatures from mutated cases, irrespectively of the cMBL or CLL condition. Overall, our study based on a prospective series of patients indicates that no major biological differences exist in cMBL compared to Rai0-CLL, suggesting that this two entities mainly differ for the initial size of the monoclonal cell population which may reflect in the longer time for clonal expansion.
Publication Title
Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A comparison of cellular, cytogenetic, molecular, and clinical features.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples