Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA116303 | ENA |
REPOSITORIES: ENA
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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
Project description:Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia
| PRJNA144311 | ENA
Project description:High-resolution genomic microarrays provides simultaneous detection of copy-number aberrations such as the known recurrent aberrations in Chronic Lymphocytic Leukemia_diagnostic sample_patient (del(11q), del(13q), del(17p) and trisomy 12), and copy-number neutral loss of heterozygosity. We screened 369 newly diagnosed Chronic Lymphocytic Leukemia_diagnostic sample_patient patient samples from a population-based cohort using 250K single nucleotide polymorphism-arrays.
2011-04-28 | GSE28030 | GEO
Project description:Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested. 10 chronic lymphocytic leukemia (CLL) samples was analyzed using four different high-resolution platforms: 32K BAC arrays, 185K Agilent oligonucleotide arrays, 250K Affymetrix SNP arrays and 317K Illumina SNP arrays.
2008-12-10 | E-GEOD-13557 | biostudies-arrayexpress
Project description:High-resolution genomic microarrays provides simultaneous detection of copy-number aberrations such as the known recurrent aberrations in Chronic Lymphocytic Leukemia_diagnostic sample_patient (del(11q), del(13q), del(17p) and trisomy 12), and copy-number neutral loss of heterozygosity. We screened 369 newly diagnosed Chronic Lymphocytic Leukemia_diagnostic sample_patient patient samples from a population-based cohort using 250K single nucleotide polymorphism-arrays. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples.
2011-04-28 | E-GEOD-28030 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. The main genetic alterations associated to this disease are loss of 13q14, loss of 11q23, trisomy 12 and, less frequently, 17p13 losses, and are routinely studied using fluorescence in situ hybridization. These genomic aberrations have been demonstrated to be important independent predictors of disease progression in CLL and their detection currently has a direct implication in the treatment strategy of the patients. It has been widely demonstrated that array-based karyotyping clearly detects DNA gains and losses and allows the identification of CLL abnormalities not included in the standard FISH panel. We have here established and tested an oligonucleotide-based array platform for the diagnosis of CLL that interrogates the most relevant chromosomal regions related with the disease and may help in the differential diagnosis between CLL and other small B-cell leukemias and may be used as a powerful prognosis tool to stratify the CLL patients. Copy number analysis using Custom Agilent 60K was performed on 47 chronic lymphocytic Leukemia patients with sex-matched control DNAs
2015-08-31 | E-GEOD-66922 | biostudies-arrayexpress
Project description:Genomic aberrations are of predominant importance to the biology and clinical outcome of patients with chronic lymphocytic leukemia (CLL), and FISH-based genomic risk classifications are routinely used in clinical decision making in CLL. One of the known limitations of CLL FISH is the inability to comprehensively interrogate the CLL genome for genomic changes. In an effort at overcoming the existing limitations in CLL genome analysis, we have analyzed high-purity DNA isolated from FACS-sorted CD19+ cells and paired CD3+ or buccal cells from 255 CLL patients for acquired genomic copy number aberrations (aCNA) using ultra-high-density Affymetrix SNP 6.0 arrays. Overall, two or more subchromosomal aCNA were found in 39% (100/255) of all cases analyzed, while ≥3 subchromosomal aCNA were detected in 20% (50/255) of cases. Subsequently, we have correlated genomic lesion loads (genomic complexity) with the clinical outcome measures time to first therapy (TTFT) and overall survival (OS). Using multivariate analyses incorporating the most important prognostic factors in CLL together with SNP 6.0 array-based genomic lesion loads at various thresholds, we identify elevated CLL genomic complexity as an independent and powerful marker for the identification of CLL patients with aggressive disease and short survival. we have analyzed high-purity DNA isolated from FACS-sorted CD19+ cells and paired CD3+ or buccal cells from 255 CLL patients for acquired genomic copy number aberrations (aCNA) using ultra-high-density Affymetrix SNP 6.0 arrays
2011-11-29 | E-GEOD-30777 | biostudies-arrayexpress
Project description:<p><b>Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation</b></p> <p>The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown since the full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains less than 20 clonally represented gene alterations/case, including predominantly non-silent mutations and fewer copy number aberrations. These analyses led to the discovery of several genes not previously known to be altered in CLL. While most of these genes were affected at low frequency in an expanded CLL screening cohort, mutational activation of NOTCH1, observed in 8.3% of CLL at diagnosis, was detected at significantly higher frequency during disease progression toward Richter transformation (31.0%) as well as in chemorefractory CLL (20.8%). Consistent with the association of NOTCH1 mutations with clinically aggressive forms of the disease, NOTCH1 activation at CLL diagnosis emerged as an independent predictor of poor survival. These results provide initial data on the complexity of the CLL coding genome and identify a dysregulated pathway of diagnostic and therapeutic relevance.</p> <p><b>Genetic Lesions associated with Chronic Lymphocytic Leukemia transformation to Richter Syndrome</b></p> <p>Richter syndrome (RS) derives from the rare transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly of the diffuse large B cell type (DLBCL). The molecular pathogenesis of RS is only partially understood. By combining whole-exome sequencing and copy-number analysis of 9 CLL-RS pairs and of an extended panel of 43 RS cases, we show that this aggressive disease typically arises from the predominant CLL clone by acquiring an average of ~20 genetic lesions/case. RS lesions are heterogeneous in terms of load and spectrum among patients, and include those involved in CLL progression and chemorefractoriness (TP53 disruption and NOTCH1 activation) as well as some not previously implicated in CLL or RS pathogenesis. In particular, disruption of the CDKN2A/B cell cycle regulator locus is associated with ~30% of RS cases. Finally, we report that the genomic landscape of RS is significantly different from that of de novo DLBCL, suggesting that they represent distinct disease entities. These results provide insights into RS pathogenesis, and identify dysregulated pathways of potential diagnostic and therapeutic relevance.</p>
| phs000364 | dbGaP
Project description:Array Comparative Genomic Hybridization (aCGH) is a widely used technique to assess chromosomal copy number alterations. Chromosomal content, however, is often not uniform throughout cell populations. The aim of our present study is to evaluate to what extent aCGH can detect DNA copy number alterations in a heterogeneous cell population. Reported detection limits are a compound of analytical software and laboratory technique whilst systematic evaluation is lacking, despite the importance in diagnostics and research. Detection limits were explored with DNA isolated from a patient with intellectual disability (ID) and from tumor cell line BT474. Both were diluted with increasing amounts of normal DNA to simulate different levels of cellularity. Samples were hybridized on CGH arrays containing 180880 oligonucleotides evenly distributed over the genome (space ~17kb). The ID sample has a single copy number gain of 4Mb and a single copy number loss of 7.5Mb that could both be detected with 10% mosaicism. The tumor cell line BT474 has a dual copy number gain (6 copies in a background of 4 copies) of 46Mb. This corresponds to a single copy number gain in a diploid sample and could be detected with 15% tumor cells. The diagnostic validity of these findings was verified using two clinical mosaic samples with alterations in 20% (40Mb) and 14% (34Mb) of cells. Both alterations could be accurately detected using t-statistics. In conclusion, single copy number gains and losses, down to 4Mb in as little as 10% of a cell population, can be detected by aCGH. DNA of a chronic lymphocytic leukemia (CLL) patient with mosaic aberrations in chromosome 12.
2012-10-21 | E-GEOD-36992 | biostudies-arrayexpress
Project description:Acquired Genomic Copy Number Aberrations and Survival in Adult Acute Myelogenous Leukemia
| PRJNA130995 | ENA