Array comparative genomic hybridization data from 313 CLL specimens to study outcome associations
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE40834 | GEO | 2013/09/07
SECONDARY ACCESSION(S): PRJNA175223
REPOSITORIES: GEO
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Project description:This study investigates genomic imbalance in chronic lymphocytic leukemia (CLL) and aims to identify genomic gains and losses with prognostic significance. Two-condition experiment, Test CLL specimens vs. Reference human genome DNA equimixture of normal male and normal female.
2013-09-07 | E-GEOD-40834 | biostudies-arrayexpress
Project description:Genomic profiles of CLL (Chronic Lymphocytic Leukemia) patients. 11 CLL patients were selected for detection of genomic aberrations, 8 patients with atypical CLL and 3 patients with typical CLL.
2009-12-16 | GSE19458 | GEO
Project description:Genomic profiles of CLL (Chronic Lymphocytic Leukemia) patients. 11 CLL patients were selected for detection of genomic aberrations, 8 patients with atypical CLL and 3 patients with typical CLL. Patient's DNA were hybridized against Promega control on Agilent G4410A arrays and scanned with the Agilent G2505B scanner.
2010-05-18 | E-GEOD-19458 | biostudies-arrayexpress
Project description:To identify genomic alterations contributing to the pathogenesis of high‑risk chronic lymphocytic leukemia (CLL) beyond the well‑established role of TP53 aberrations, we comprehensively analyzed 146 high‑risk CLL cases by single‑nucleotide polymorphism (SNP)‑arrays and targeted next‑generation sequencing including 75 relapsed/refractory and 71 treatment‑naïve high‑risk cases from prospective clinical trials. Increased genomic complexity was a hallmark of relapsed/refractory and treatment‑naïve high‑risk CLL, and was associated with TP53 and ATM dysfunction. In relapsed/refractory cases previously exposed to the selective pressure of chemo(immuno)therapy, gain(8)(q24.21) and del(9)(p21.3) were found particularly enriched. Both of these copy number alterations (CNAs) affected key regulators of cell cycle progression, namely c‑MYC and CDKN2A/B. Gains in 8q24.21 were either focal gains in a c‑MYC enhancer region or larger gains directly affecting the c‑MYC locus, but only the latter type was highly enriched in relapsed/refractory CLL (17%). Loss of CDKN2A/B was found frequently to co‑occur with gain of c‑MYC and in this combination it was likely associated with Richter transformation. In addition to a high frequency of NOTCH1 mutations (23%), we found recurrent genetic alterations in SPEN (4% mutated), RBPJ (8% deleted) and SNW1 (8% deleted), all affecting a protein complex that represses transcription of NOTCH1 target genes. We investigated the functional impact of these alterations on HES1, DTX1 and c‑MYC gene transcription and found de‑repression of these NOTCH1 target genes particularly with SPEN mutations. In summary, we provide new insights into the pathogenesis of high‑risk CLL by defining novel recurrent CNAs and identifying alterations that likely contribute to disease refractoriness.
2020-05-06 | GSE131114 | GEO
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:We examined copy number changes in the genomes of B cells from 58 patients with chronic lymphocytic leukemia (CLL) using representational oligonucleotide microarray analysis (ROMA), a form of comparative genomic hybridization (CGH), at a resolution exceeding previously published studies. We observed at least one genomic lesion in each CLL sample and considerable variation in the number of abnormalities from case to case. Virtually all abnormalities previously reported were also observed here, most of whichwere indeed highly recurrent. We observed the boundaries of known events with greaterclarity and identified previously undescribed lesions, some of which were recurrent. Weprofiled the genomes of CLL cells separated by the surface marker CD38, and foundevidence of distinct subclones of CLL within the same patient. We discuss the potential applications of high resolution CGH analysis in a clinical setting. Keywords: Genetic modification, polymorphonuclear cell (PMN)
2008-10-01 | GSE12794 | 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:Many functional consequences of mutations on tumor phenotypes in chronic lymphocytic leukemia (CLL) are only partially known. This is in part due to a scarcity of information on the proteome of CLL. We profiled the proteome of 117 CLL samples with data-independent acquisition mass spectrometry (DIA-MS) and integrated the results with genomic, transcriptomic, functional data and clinical outcome. We found trisomy 12 and IGHV to be major determinants of proteome variation in CLL (1055 and 542 differential proteins FDR of 5%). Trisomy 12 was associated with limited protein abundance buffering. Protein complex analyses detected functional units involved in BCR/PI3K/AKT signaling in CLL with trisomy 12. We associated protein expression with response to anticancer drugs, and STAT2 protein expression emerged as a biomarker for the prediction of response to kinase inhibitors including BTK and MEK inhibitors. STAT2 protein levels were determined by gene dosage (trisomy 12), stabilization in a protein complex and linked to interferon signaling in CLL. This study highlights the emerging importance of protein abundance profiling in CLL biology.
2021-09-24 | PXD022198 | Pride
Project description:Purpose: The chromosomal deletion 11q affects biology and clinical outcome in CLL but del11q-deregulated genes remain incompletely characterized. Results: We have identified differential expression of the insulin receptor (INSR) in CLL, including high-level INSR expression in the majority of CLL with del11q. High INSR mRNA expression in 11q CLL (~10-fold higher mean levels than other genomic categories) was confirmed by Q-PCR in 247 CLL cases. INSR protein measurements in 257 CLL cases through FACS, compared with measurements in normal CD19+ B-cells and monocytes, confirmed that a subset of CLL aberrantly expresses high INSR levels.
2011-05-06 | GSE26526 | GEO
Project description:Purpose: The chromosomal deletion 11q affects biology and clinical outcome in CLL but del11q-deregulated genes remain incompletely characterized. Results: We have identified differential expression of the insulin receptor (INSR) in CLL, including high-level INSR expression in the majority of CLL with del11q. High INSR mRNA expression in 11q CLL (~10-fold higher mean levels than other genomic categories) was confirmed by Q-PCR in 247 CLL cases. INSR protein measurements in 257 CLL cases through FACS, compared with measurements in normal CD19+ B-cells and monocytes, confirmed that a subset of CLL aberrantly expresses high INSR levels. We have employed integrated genomic profiling approaches upon CLL cases with and without del11q to identify 11q-relevant genes. Included are 10 primary human cases with del11q and 9 cases without del11q
2011-05-05 | E-GEOD-26526 | biostudies-arrayexpress