Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia – unexpected expression pattern of the RHO GTPase activator ARHGAP20
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE25571 | GEO | 2011/10/14
SECONDARY ACCESSION(S): PRJNA133883
REPOSITORIES: GEO
Similar Datasets
Project description:In chronic lymphocytic leukemia (CLL), 13q14 and 11q22-23 deletions are found in 2/3 of the cases. 11q22-23 deletions are associated with poor survival, whereas 13q14 deletions as single abnormality are often found in indolent disease forms. The molecular basis for this difference in prognosis is not known. ARHGAP20 encodes an evolutionarily conserved protein. In the zebra fish (Danio rerio) genome the syntenic regions of human chromosomal bands 13q14 and 11q22-23 are juxtaposed. The similar expression profiles of ARHGAP20 in 13q14 and 11q22-23 deleted CLL cases suggest a molecular connection and an intriguing mechanism of regulation. Analysis of 154 samples of peripheral blood mononuclear cells (109 HGU-133plus2; 45 HGU-133A; 45 HGU-133B) from adult patients with chronic lymphocytic leukemia (CLL).
2011-10-13 | E-GEOD-25571 | biostudies-arrayexpress
Project description:Recent GWAS have identified several susceptibility loci for NHL. Despite these successes, much of the heritable variation in NHL risk remains to be explained. Common copy-number variants are important genomic sources of variability, and hence a potential source to explain part of this missing heritability. In this study, we carried out a CNV analysis using GWAS data from 681 NHL cases and 749 controls to explore the relationship between common structural variation and lymphoma susceptibility. Here we found a novel association with diffuse large B-cell lymphoma (DLBCL) risk involving a partial duplication of the C-terminus region of the LOC283177 long non-coding RNA that was further validated by quantitative PCR. For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), known somatic deletions were identified on chromosomes 13q14, 11q22-23, 14q32 and 22q11.22. Our study shows that GWAS data can be used to identify germline CNVs associated with disease risk for DLBCL and somatic CNVs for CLL/SLL.
2014-09-23 | GSE58718 | GEO
Project description:Recent GWAS have identified several susceptibility loci for NHL. Despite these successes, much of the heritable variation in NHL risk remains to be explained. Common copy-number variants are important genomic sources of variability, and hence a potential source to explain part of this missing heritability. In this study, we carried out a CNV analysis using GWAS data from 681 NHL cases and 749 controls to explore the relationship between common structural variation and lymphoma susceptibility. Here we found a novel association with diffuse large B-cell lymphoma (DLBCL) risk involving a partial duplication of the C-terminus region of the LOC283177 long non-coding RNA that was further validated by quantitative PCR. For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), known somatic deletions were identified on chromosomes 13q14, 11q22-23, 14q32 and 22q11.22. Our study shows that GWAS data can be used to identify germline CNVs associated with disease risk for DLBCL and somatic CNVs for CLL/SLL. We performed a genome-wide CNV analysis of 681 NHL cases and 749 controls from the San Francisco Bay Area, genotyped using the Illumina HumanCNV370-Duo BeadChip array. Signal intensity data in the form of log R ratio (LRR) and B allele frequency (BAF) values were obtained directly from the Beadstudio software. Quality control filtering was used to exclude unreliable samples, resulting in a final dataset of 619 NHL cases (205 FL, 242 DLBCL, 172 CLL/SLL) and 730 controls.
2014-09-23 | E-GEOD-58718 | biostudies-arrayexpress
Project description:We used high density oligonucleotide arrays to identify molecular correlates of genetically and clinically distinct subgroups of B-cell chronic lymphocytic leukemia (B-CLL). Gene expression profiling was used to profile the five most frequent genomic aberrations, namely deletions affecting chromosome bands 13q14, 11q22-q23, 17p13 and 6q21, and gains of genomic material affecting chromosome band 12q13. A strikingly high degree of correlation between loss or gain of genomic material and the amount of transcripts from the affected regions leads to the hypothesis of gene dosage as a significant pathogenic factor. Furthermore, the influence of the immunoglobulin variable heavy chain (VH) mutation status was determined. A clear distinction in the expression profiles of unmutated and mutated VH samples exists, which can be discovered using unsupervised learning methods. However, when samples were separated by gender, this separation could only be detected in samples from male patients. Since the samples were either hybridized onto HG-U95A arrays or onto HG-U95Av2 arrays, only genes common to both arrays were used for further analysis. This study is described in more detail in Haslinger C, et al. 2004. J Clin Oncol. 22:3937-3949; Series _keyword: CLL, chronic lymphocytic leukemia, immunoglobulin somatic hypermutation, genomic aberrations
2007-08-25 | E-GEOD-2466 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness with a variable clinical course. Loss of chromosomal material on chromosome 13 at cytoband 13q14 is the most frequent genetic abnormality in CLL, but the molecular aberrations underlying del13q14 in CLL remain incompletely characterized. We analyzed 171 CLL cases for LOH and sub-chromosomal copy loss on chromosome 13 in DNA from FACS-sorted CD19+ cells and paired buccal cells using the Affymetrix XbaI 50K SNP-array platform. The resulting high-resolution genomic maps, together with array-based measurements of expression levels of RNA in CLL cases with and without del13q14 and Q-PCR-based expression analysis of selected genes support the following conclusions: i) del13q14 is heterogeneous and composed of multiple subtypes with deletion of Rb or the miR15a/16 loci serving as anatomic landmarks, respectively ii) del13q14 type Ia deletions are relatively uniform in length and extend from breakpoints close to the miR15a/16 cluster to a newly identified telomeric breakpoint cluster at ~50.2-50.5 Mb physical position iii) LATS2 RNA levels are ~2.6-2.8-fold lower in cases with del13q14 type I that do not delete Rb as opposed to all other CLL cases and iv) ~15% of CLL cases display marked reductions in miR15a/16 expression often but not invariably associated with bi-allelic miR15a/16 loss. This data should aid future investigations into biological differences imparted on CLL by different del13q14 subtypes including investigations into LATS2 as one of the genes found deregulated as part of del13q14. Keywords: Chronic lymphocytic leukemia, CLL, gene expression comparison, del13q14, del13q
2007-10-06 | GSE9250 | GEO
Project description:Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness with a variable clinical course. Loss of chromosomal material on chromosome 13 at cytoband 13q14 is the most frequent genetic abnormality in CLL, but the molecular aberrations underlying del13q14 in CLL remain incompletely characterized. We analyzed 171 CLL cases for LOH and sub-chromosomal copy loss on chromosome 13 in DNA from FACS-sorted CD19+ cells and paired buccal cells using the Affymetrix XbaI 50K SNP-array platform. The resulting high-resolution genomic maps, together with array-based measurements of expression levels of RNA in CLL cases with and without del13q14 and Q-PCR-based expression analysis of selected genes support the following conclusions: i) del13q14 is heterogeneous and composed of multiple subtypes with deletion of Rb or the miR15a/16 loci serving as anatomic landmarks, respectively ii) del13q14 type Ia deletions are relatively uniform in length and extend from breakpoints close to the miR15a/16 cluster to a newly identified telomeric breakpoint cluster at ~50.2-50.5 Mb physical position iii) LATS2 RNA levels are ~2.6-2.8-fold lower in cases with del13q14 type I that do not delete Rb as opposed to all other CLL cases and iv) ~15% of CLL cases display marked reductions in miR15a/16 expression often but not invariably associated with bi-allelic miR15a/16 loss. This data should aid future investigations into biological differences imparted on CLL by different del13q14 subtypes including investigations into LATS2 as one of the genes found deregulated as part of del13q14. Experiment Overall Design: The goal of this analysis is to detect probesets that are differentially expressed between CLL patients with wild type chromosome 13 and 13q-deleted samples. There are a total of 20 arrays.
2008-06-16 | E-GEOD-9250 | biostudies-arrayexpress
Project description:We used high density oligonucleotide arrays to identify molecular correlates of genetically and clinically distinct subgroups of B-cell chronic lymphocytic leukemia (B-CLL). Gene expression profiling was used to profile the five most frequent genomic aberrations, namely deletions affecting chromosome bands 13q14, 11q22-q23, 17p13 and 6q21, and gains of genomic material affecting chromosome band 12q13. A strikingly high degree of correlation between loss or gain of genomic material and the amount of transcripts from the affected regions leads to the hypothesis of gene dosage as a significant pathogenic factor. Furthermore, the influence of the immunoglobulin variable heavy chain (VH) mutation status was determined. A clear distinction in the expression profiles of unmutated and mutated VH samples exists, which can be discovered using unsupervised learning methods. However, when samples were separated by gender, this separation could only be detected in samples from male patients. Since the samples were either hybridized onto HG-U95A arrays or onto HG-U95Av2 arrays, only genes common to both arrays were used for further analysis. This study is described in more detail in Haslinger C, et al. 2004. J Clin Oncol. 22:3937-3949 Series _keyword: CLL, chronic lymphocytic leukemia, immunoglobulin somatic hypermutation, genomic aberrations Keywords: other
2005-04-01 | GSE2466 | GEO
Project description:To identify genomic alterations in chronic lymphocytic leukemia (CLL), we performed single-nucleotide polymorphism (SNP)-array analysis on 353 samples from previously untreated patients entered on the CLL8 treatment trial. Based on paired-sample analysis (n=147), a mean of 1.8 copy number alterations (CNAs) per case were identified; about 60% of cases carried no CNAs other than those detected by routine fluorescence in-situ hybridization analysis. Copy-neutral loss-of- heterozygosity was detected in 6% of cases, and most frequently found on 13q, 17p and 11q. Minimal deleted regions (MDRs) were refined on 13q14 (deleted in 61% of cases) to the DLEU1 and DLEU2 genes, on 11q22.3 (27%) to ATM, on 2p (gained in 7% of cases) to a 1.9 Mb fragment containing 9 genes, and on 8q24 (5%) to a segment 486 Kb proximal of the MYC locus. 13q deletions exhibited proximal and distal breakpoint cluster regions. Among the most common novel lesions were deletions at 15q15.1 (4%), with the smallest deletion (70.5 Kb) found in the MGA locus; sequence analysis of MGA in 59 samples revealed a truncating mutation in one case lacking a 15q deletion. MNT at 17p13.3, which in addition to MGA and MYC encodes for the network of MAX-interacting proteins, was also found recurrently deleted. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic peripheral blood samples. Copy number analysis of Affymetrix® performed for 353 CLL samples. There are also 147 samples from mononuclear cells negative for CD19, which were used as references for copy number inference.
2012-10-11 | E-GEOD-36908 | biostudies-arrayexpress
Project description:With an objective to identify novel copy number alterations (CNAs) critical to CLL pathogenesis, we performed array comparative genomic hybridization (array CGH) on genomic DNA extracted from purified leukemic cells of 51 CLL patients. We used the 1.4 Mb HumArray platform, and analyzed data using a combination of three different statistical algorithms and in full awareness of the copy number variations (CNVs) found in normal populations. Use of reference DNA extracted from matched patient neutrophils in four cases also assisted a more comprehensive interpretation of constitutional versus CLL-specific copy number alterations. A total of 108 clones showed alterations in >10% of the cases. Of these, 25 clones corresponded to known recurrently acquired CNAs for CLL, representing +12 in 8 cases (16%) and del(13)(q14) in 26 cases (51%). For the remaining 83 clones, frequent deletions corresponded to loci within cytobands 17q12 (71% of CLL cases), 9q32 (55%), 8p23 (47%) and 2q21 (33%), and frequent gains corresponded to loci within cytobands 18q22.3 (51%), 20p12 (33%) and 15q13 (31%), most of which have been reported in normal population cohorts. We further analysed associations between CNV status across the 108 frequently affected clones and CD38 expression status. Consistent with previous findings, loss of 13q14 (represented in clone RPI-269F22) and gain of chromosome 12 (clones RP11-64J22, RMC12P001 and RP11-282G15) were associated with low and high CD38 expression, respectively. We also found that loss within the beta-defensin (DEFB) locus at 8p23, and gains across clones CTB-120N12 (17q25) and RP11-118K20 (13q31.1) were associated with the poor prognostic CD38+ subgroup (p<0.05). Further studies are needed to assess biological relevance of genes located within these regions and prognostic outcomes in CLL.
2017-06-14 | GSE21998 | GEO
Project description:It has been widely recognized that a 13q14 deletion is often found in CLL and that this deletion is associated with a good prognosis. Such deletions are sometime detected only by fluorescence in situ hybridization (FISH) [1] because they are too small to be detected by banding. We report here a small deletion that is undetectable by FISH but identifiable by high-resolution comparative genomic hybridization (CGH) arrays. A 62-year-old patient with previously untreated chronic lymphocytic leukemia (CLL; BinetÕs stage A) was studied because of a recent increase of his lymphocyte counts. The patient had been in stage A since the initial diagnosis was made 12 years before. At the time of cytogenetic analysis, the peripheral lymphocyte count was 65.3 g/L with weak llight chain surface imunoglobulin expression and a Matutes score of 5/5. The karyotype of 12-O-tetradecanoylphorbal 13-acetate-stimulated blood cells was 46,X,-Y[3]/46,XY [17]. FISH with X and Y probes confirmed that 90% of the blood cells had a Y chromosome loss, which is an infrequent but recurrent finding in CLL. FISH of 200 cells found no 13q14 deletion.
2008-06-09 | E-TABM-293 | biostudies-arrayexpress