Molecular and transcriptional characterization of chromosome 17p loss in chronic lymphocytic leukemia
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PROVIDER: PRJNA107133 | ENA |
REPOSITORIES: ENA
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Project 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. This SuperSeries is composed of the following subset Series: GSE9992: Molecular and transcriptional characterization of chromosome 17p loss in chronic lymphocytic leukemia, experiment A GSE11036: Molecular and transcriptional characterization of chromosome 17p loss in chronic lymphocytic leukemia, experiment B Keywords: SuperSeries Refer to individual Series
2008-11-11 | E-GEOD-11038 | biostudies-arrayexpress
Project 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. This SuperSeries is composed of the SubSeries listed below.
2008-11-11 | GSE11038 | GEO
Project 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. Keywords: genomic analysis of B-CLL with 17p loss patients
2008-11-11 | GSE11036 | GEO
Project 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. Keywords: transcriptional analysis of B-CLL with 17p loss patients
2008-11-11 | GSE9992 | GEO
Project 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. Keywords: transcriptional analysis of B-CLL with 17p loss patients This series of microarray experiments contains the gene expression profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 60 newly diagnosed patients (Binet stage A). Peripheral blood mononuclear cells from B-CLL patients were isolated by Ficoll-Hypaque density-gradient centrifugation and the proportion of CD5/CD19/CD23 triple positive B cells in the suspension was determined by direct immunofluorescence performed using a FACS-sort flow cytometer with antibodies to: CD19 FITC/PE, CD23 PE and CD5 Cy-Chrome. If B-CLL cells were less than 90%, T cells, NK cells and monocytes were removed by negative selection using CD3, CD56, CD16, and CD14 monoclonal antibody treatment followed by magnetic beads. 3 micrograms of total RNA was processed and, in accordance with the manufacturer's protocols, 15 micrograms of fragmented biotin-labelled cRNA were hybridized on GeneChip Human Genome U133A 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) and the probe level data converted to expression values using the Bioconductor function for the Robust Multi-Array average (RMA) procedure (Irizarry et al, 2003), in which perfect match intensities are background adjusted and quantile-quantile normalised.
2008-11-11 | E-GEOD-9992 | biostudies-arrayexpress
Project 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. Keywords: genomic analysis of B-CLL with 17p loss patients This series of microarray experiments contains the genome-wide profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 12 newly diagnosed patients (Binet stage A). Peripheral blood mononuclear cells from B-CLL patients were isolated by Ficoll-Hypaque density-gradient centrifugation and the proportion of CD5/CD19/CD23 triple positive B cells in the suspension was determined by direct immunofluorescence performed using a FACS-sort flow cytometer with antibodies to: CD19 FITC/PE, CD23 PE and CD5 Cy-Chrome. If B-CLL cells were less than 90%, T cells, NK cells and monocytes were removed by negative selection using CD3, CD56, CD16, and CD14 monoclonal antibody treatment followed by magnetic beads. 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 1 Mb, and inferred copy number states were derived from a Hidden Markov Model (HMM) based algorithm implemented in CNAT 4.0.1.
2008-11-11 | E-GEOD-11036 | biostudies-arrayexpress
Project description:We performed whole genome profiling in order to determine the landscape of genetic alterations assoicated with a subset of CLL that is characterized by deletions in 17p The number of copy number alterations predicted shorter time to treatment among patients untreated at sampling. Chromosome 3p, 4p, and 9p were frequently deleted in del(17p) CLL and strongly associated with shorter OS. We conclude that del(17p) has a unique genomic profile characterized typically by TP53 mutation with novel CNAs and novel drivers, with increasing genomic complexity of any type associated with worse overall survival.
2016-10-21 | GSE74239 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE38611: Relevance of Chromosome 2p Gain in Early Binet Stage A Chronic Lymphocytic Leukemia (expression) GSE38613: Relevance of Chromosome 2p Gain in Early Binet Stage A Chronic Lymphocytic Leukemia (SNP) Refer to individual Series
2012-10-12 | E-GEOD-38618 | biostudies-arrayexpress
Project description:Chromosome copy number variations are a hallmark of human cancers and among them chromosome 17p loss is the most common one and associated with poor prognosis. Our previous work demonstrates that 17p deletions can promote tumorigenesis more than p53 loss. Herein, with multiple functional genetic strategies, we identify a new 17p tumor suppressor, PHD finger protein 23 (PHF23). PHF23 deficiency impaires B cell differentiation and promotes Myc-driven lymphoma. Mechanistically, PHF23, a H3K4me3 reader, directly binds and represses the deacetylation activity of the SIN3-HDAC complex through its N-terminus, which coordinates two major active histone markers H3K4me3 and H3K27ac for activation of downstream B cell-differentiation genes and tumor suppressors. Further, we show that dysregulation of the PHF23-SIN3-HDAC complex is essential for PHF23 deficiency-induced tumorigenesis and maintenance. Hence, our study reveals a novel epigenetic regulatory mechanism that contributed to the pathology of 17p deleted cancers and suggests novel susceptibility of this miserable disease.
2020-12-20 | GSE145190 | GEO
Project description:Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients. Single nucleotide polymorphism (SNP)-arrays allow simultaneous detection of copy-number aberrations (CNAs) and copy-number neutral loss-of-heterozygosity (CNN-LOH). In this study we investigated the presence of CNAs and CNN-LOH in newly diagnosed CLL samples from a Swedish chronic lymphocytic leukemia (CLL) cohort. In this study we could detect the known recurrent aberrations in CLL (i.e. deletions of 13q, 11q, 17p and trisomy 12). We also detected other both large and small CNAs which were mostly non-recurrent. CNN-LOH was detected on chromosome 13q in patients that carried homozygous deletion of 13q.
2009-11-23 | GSE16406 | GEO