Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA147873 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To identify cooperating lesions in core-binding-factor acute myeloid leukemia (CBF-AML), we performed single-nucleotide polymorphism (SNP)-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations (CNAs) per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDRs) were identified at 7q36.1 (7.7%), 9q21.13 (5%), 11p13 (2.3%), and 17q11.2 (2%). Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single non-coding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%), with known mutated cancer genes present in the minimally altered region. Analysis of relapse samples identified recurrent MDRs at 3q13 (12.2%), 5q (4.9%), and 17p (4.9%). SNP genotyping was performed on 300 adult and pediatric CBF-AMLs; t(8;21), n=157 (adult, n=114; pediatric, n=43); and inv(16), n=143 (adult, n=104; pediatric, n=39). Germline control DNA from remission bone marrow or peripheral blood was available for paired analysis in 175 patients. In addition, for 41 patients, matched relapse samples were analyzed. Data were processed using reference alignment, dChipSNP and circular binary segmentation.
2012-02-07 | E-GEOD-32462 | biostudies-arrayexpress
Project description:To identify cooperating lesions in core-binding-factor acute myeloid leukemia (CBF-AML), we performed single-nucleotide polymorphism (SNP)-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations (CNAs) per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDRs) were identified at 7q36.1 (7.7%), 9q21.13 (5%), 11p13 (2.3%), and 17q11.2 (2%). Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single non-coding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%), with known mutated cancer genes present in the minimally altered region. Analysis of relapse samples identified recurrent MDRs at 3q13 (12.2%), 5q (4.9%), and 17p (4.9%).
2012-02-07 | GSE32462 | GEO
Project description:High-Resolution Genomic Profiling of Chronic Lymphocytic Leukemia Reveals New Recurrent Genomic Alterations
| PRJNA158401 | ENA
Project description:Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with both pediatric and adult leukemia. However, the treatment options for these aggressive MLLr leukemias are limited due to the genomic complexity and dynamics of 3D structure in oncogene transcription and leukemia development. Here, we use Micro-C and transcriptome profiling to examine the MLLr-driven aberrant 3D genome architecture in gene-edited MLL-AF9 AML samples with biologically matched healthy donors. Recurrent and MLLr-specific alterations in A/B compartments, topologically associating domains and chromatin loops were identified. RNA sequencing in the same AML samples also revealed extensive and recurrent MLLr-specific promoter–enhancer and promoter–silencer loops. Overall, this study highlights the critical regulatory elements and provides rational and effective targeting strategy in MLLr AML.
2024-02-20 | GSE244471 | GEO
Project description:Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with both pediatric and adult leukemia. However, the treatment options for these aggressive MLLr leukemias are limited due to the genomic complexity and dynamics of 3D structure in oncogene transcription and leukemia development. Here, we use Micro-C and transcriptome profiling to examine the MLLr-driven aberrant 3D genome architecture in gene-edited MLL-AF9 AML samples with biologically matched healthy donors. Recurrent and MLLr-specific alterations in A/B compartments, topologically associating domains and chromatin loops were identified. RNA sequencing in the same AML samples also revealed extensive and recurrent MLLr-specific promoter–enhancer and promoter–silencer loops. Overall, this study highlights the critical regulatory elements and provides rational and effective targeting strategy in MLLr AML.
2024-02-20 | GSE244470 | GEO
Project description:Identification of Acquired Copy Number Alterations and Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia Using High-Resolution Single Nucleotide Polymorphism Analysis Recent advances in genome-wide single nucleotide polymorphism (SNP) analyses have revealed previously unrecognized microdeletions and uniparental disomy (UPD) in a broad spectrum of human cancers. As acute myeloid leukemia (AML) represents a genetically heterogeneous disease, this technology might prove helpful especially for cytogenetically normal AML (CN-AML) cases. Thus, we performed high-resolution SNP analyses in 157 adult cases of CN-AML. Regions of acquired UPD were identified in 12% of cases and most frequently affected chromosomes 6p, 11p, and 13q. Notably, acquired UPD was invariably associated with mutations in NPM1 or CEBPA that impair hematopoietic differentiation (P=0.008), suggesting that UPDs may preferentially target genes that are essential for proliferation and survival of hematopoietic progenitors. Acquired copy number alterations (CNAs) were detected in 49% of cases with losses found in two or more cases affecting e.g. chromosome bands 3p13-p14.1 and 12p13. Furthermore, we identified two cases with a cryptic t(6;11) as well as several non-recurrent aberrations pointing to leukemia relevant regions. With regard to clinical outcome, there appeared to be an association between UPD 11p and UPD 13q cases with overall survival. These data demonstrate the potential of high-resolution SNP analysis for identifying genomic regions of potential pathogenic and clinical relevance in AML.
2009-12-01 | GSE19101 | GEO
Project description:To ascertain genomic alterations associated with Imatinib resistance in chronic myeloid leukaemia, we performed high resolution genomic analysis of CD34+ cells from 25 Imatinib (IM) resistant and 11 responders CML patients. Using patients' T-cells as reference, we found significant association between number of acquired cryptic copy number alterations (CNA) and disease phase (p=0.036) or loss of IM response for patients diagnosed in chronic phase (CP) (p=0.04). Recurrent cryptic losses were identified on chromosomes 7, 12 and 13. On chromosome 7, recurrent deletions of the IKZF1 locus were detected, for the first time, in four patients in CP. Patients suffering from chronic myeloid leukaemia were compared using CD34+ cells and T cells as reference and hybridized on Agilent-014698 Whole Human Genome 105K microarrays.
2010-11-15 | E-GEOD-21986 | biostudies-arrayexpress
Project description:<p>Pediatric <i>de novo</i> acute myeloid leukemia (AML) is a heterogeneous disease that can be divided into clinically distinct subtypes based on the presence of specific chromosomal abnormalities or gene alterations. One of the best characterized subtypes of AML involves leukemias with alterations of the core-binding factor (CBF)-complex, which comprises the FAB subtypes M2 and M4Eo and associates with a favorable outcome. Patients with the AML M2 subtype harbor a translocation between chromosomes 8 and 21 [t(8;21)] that yields the chimeric fusion gene <i>RUNX1(AML1)-RUNX1T1(ETO)</i>, while patients with AML M4Eo express the chimeric fusion gene <i>CBFβ-SMMHC(MYH11)</i> as a result of an inversion/translocation event of chromosome 16 [inv(16)/t(16;16)]. In an effort to define the total complement of genetic changes in CBF-leukemia, we performed paired-end whole genome sequencing (WGS) on diagnostic leukemia blasts and matched germ line samples from 17 pediatric CBF-leukemia patients using the Illumina platform. Somatic alterations, including single nucleotide variations (SNVs) and structural variations (SVs), including insertions, deletions, inversions, and inter- and intra-chromosomal rearrangements, were detected using complementary analysis pipelines (Bambino, CREST and CONSERTING). Recurrent screening of identified mutations will be performed in a cohort of approximately 94 cases of CBF-leukemias.</p>
| phs000414 | dbGaP
Project description:Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics.
2023-09-26 | PXD043982 | Pride
Project description:To identify cooperating lesions in de novo and therapy-related acute myeloid leukemia (t-AML) with translocation t(9;11)(p22;q23) we performed high-resolution SNP-array profiling on 40 leukemia samples [de novo: n=22; t-AML: n=16; unknown: n=2]. A mean of 1.73 copy number alterations (CNAs)/case were identified with no differences between de novo and t-AML cases. We identified a novel minimally deleted region (MDR) at 7q36.1-q36.2 partly overlapping with a MDR previously identified in core-binding factor AML; MLL3 was the only gene affected in both regions. In addition, a recurrent gain was found at 13q21.33-q22.1 harboring the potential oncogene KLF5. Sequence/expression analysis of selected candidate genes revealed deregulated EVI1 at high frequency (50%). Copy-neutral loss-of-heterozygosity (CN-LOH) was absent in the paired cohort Further analysis of the candidate genes might provide novel insights into the pathogenesis of t(9;11) AML SNP genotyping was performed on 40 de novo and therapy-related MLL-MLLT3-rearranged acute myeloid leukemia samples; Germline control DNA from remission bone marrow or peripheral blood was available for paired analysis in 15 patients. Data were processed using reference alignment, dChipSNP and circular binary segmentation.
2014-05-22 | E-GEOD-46745 | biostudies-arrayexpress