Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA299779 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The chromosomal translocation t(12;21) resulting in the ETV6-RUNX1 fusion gene is the most common genetic abnormality in childhood acute lymphoblastic leukemia (ALL). As the emergence of microarray technology, finding subtype-specific genes becomes one of the main objectives in most ALL studies. However, the list of differentiated genes derived by comparing patients in the subtype versus the others contains many false positives, which are not really subtype-specific. In order to refine the list of subtype-specific genes for ALL with ETV6-RUNX1, this study conducted microarray experiments on patients in both diagnosis and remission status.
2019-02-01 | GSE74335 | GEO
Project description:The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q), and +16 as possible early events in the leukemogenic process. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from 23 leukemic bone marrow samples and one ETV6/RUNX1-positive cell line.
2010-07-07 | E-GEOD-19996 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) play important roles in numerous diseases and represent an emerging layer of cancer biology. However, the role that lncRNAs play in the pathogenesis of pediatric B-cell leukemia (B-ALL) with t(12;21) (ETV6-RUNX1) translocation is largely unknown. In this study, we assessed the lncRNA expression profiles of 42 pediatric B-ALL (24 with and 18 without the t(12;21) translocation) and 4 bone marrows from healthy donors. We identified 117 lncRNAs that were differentially expressed (fold change> 1.5 and FDR > 0.05) between the B-ALL subgroups (ETV6-RUNX1-positive and ETV6-RUNX1-negative). The most upregulated lncRNAs in ETV6-RUNX1 positive B-ALL were TCL6, RP4-697K14.3, LOC100292680, RP11-345I18.1, LINC00599 and TRAF3IP2-AS1, while the most downregulated were RP11-135F9.1, RP11-561B11.1, AK095221, RP11-463H12.1, AC007283.4 and CCDC26. Coding-non-coding gene co-expression networks were constructed to identify lncRNAs with potential functions in ETV6-RUNX1 translocation. Levels of representative lncRNA-mRNA pairs were further detected by RT-qPCR in patients with pediatric B-ALL. Importantly, pediatric B-ALL patients who expressed low levels of the lncRNA TCL6 had lower disease-free survival than patients with high levels of TCL6. Thus, these findings provide the first detailed description of lncRNA expression profiles related to t(12;21) translocation in pediatric B-ALL. Such lncRNAs profiles might play important roles in driving normal cells to leukemic cells. These lncRNAs may provide novel molecular biomarkers and offer new basis for combating pediatric B-ALL.
2019-12-10 | GSE128254 | GEO
Project description:Analysis of gene signatures in WT+Ctrl vs WT+ETV6-RUNX1, Btg1-/- and Btg1-/-+ETV6-RUNX1 in cKit+Ter119- fetal liver-derived hematopoietic progenitor cells (FL-HPCs). The Btg1-/-+ETV6-RUNX1 FL-HPCs display a strong increase in proliferation compared to WT+ETV6-RUNX1. Total RNA otained from WT+Ctrl, WT+ETV6-RUNX1, Btg1-/-+Ctrl and Btg1-/-+ETV6-RUNX1 FL-HPCs cells that were cultured for 12 days in expansion medium.
2014-08-22 | E-GEOD-60589 | biostudies-arrayexpress
Project description:ETV6-RUNX1 is a first-hit mutation in childhood B cell precursor acute lymphoblastic leukaemia. ETV6-RUNX1 is a fusion protein which inherits the DNA-binding runt domain from RUNX1. Here we performed chromatin precipitation for native RUNX1 and ETV6-RUNX1 using RUNX1 antibodies and specifically for the ETV6-RUNX1 fusion using a V5-tag pull down.
2022-10-31 | E-MTAB-12208 | biostudies-arrayexpress
Project description:B-cell precursor acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer. Although the genetic origin of the disease remains unclear, epigenetic modifications including DNA methylation are suggested to contribute significantly to leukemogenesis. We assessed the DNA methylation status of 402,842 CpG-sites across the genome (Illumina 450k array) in tumor and remission samples of 46 pre-B ALL patients, thus generating the most comprehensive single CpG-site resolution pre-B ALL methylomes so far. Unsupervised hierarchical clustering of CpG-site neighborhood, protein-coding gene, or miRNA gene associated methylation levels separated the tumor cohort according to major pre-B ALL subtypes, and methylation in CpG islands, shores, and in regions around the transcription start site of protein-coding genes strongly correlated with transcript expression. Focusing on samples carrying the t(12;21)(p13;q22) translocation (ETV6-RUNX1 fusion gene) we identified subtype-specific methylation of 430 CpG-sites. Pathway analyses implied the associated genes in hematopoiesis and cancer. Further intersection with transcriptome data identified methylation to impact expression of 18 genes. In summary, our data illustrate the power of methylation profiling to classify leukemic subtypes and to identify subtype-specific methylation markers. Further, we demonstrate that integration of methylome and transcriptome alterations allows the study of downstream effects of individual genomic rearrangements in cancer. Bisulfite converted DNA of tumor (isolated on day of diagnosis) and remission (isolated after disease remission) samples derived from 46 patients of French-Canadian origin diagnosed with pre-B ALL were analyzed on the Illumina Infinium HumanMethylation 450k BeadChips.
2013-06-04 | E-GEOD-38235 | biostudies-arrayexpress
Project description:RUNX1 and ETV6-RUNX1 possess the same DNA-binding runt domain and are therefore expected to bind to canonical RUNX motifs. As the ETV6-RUNX1 fusion arises in the context of native RUNX1 expression, and since RUNX1 is retained or amplified in B-ALL, the two proteins are likely to compete for the same target sites. To assess this, we performed RUNX1 ChIP-seq in the presence of exogenous ETV6-RUNX1 (or non DNA binding ETV6-RUNX1-R139G) and the reciprocal experiment: ETV6-RUNX1 ChIP (using a V5 tag) in the presence of exogenous RUNX1 or vector control.
2022-10-31 | E-MTAB-12209 | biostudies-arrayexpress
Project description:Analysis of gene signatures in WT+Ctrl vs WT+ETV6-RUNX1, Btg1-/- and Btg1-/-+ETV6-RUNX1 in cKit+Ter119- fetal liver-derived hematopoietic progenitor cells (FL-HPCs). The Btg1-/-+ETV6-RUNX1 FL-HPCs display a strong increase in proliferation compared to WT+ETV6-RUNX1.
2014-08-22 | GSE60589 | GEO
Project description:The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q), and +16 as possible early events in the leukemogenic process.
2010-07-07 | GSE19996 | GEO
Project description:Distal enhancers play critical roles in sustaining oncogenic gene expression programs. We obtained ATAC-Seq data and ChIP-Seq data using antibodies against the H3K27ac histone mark, transcription factors ERG and ETV6, and input chromatin from B-ALL cell lines and comparator B-cell cancer cell lines, including B-ALL with biallelic ETV6 inactivation, ETV6-RUNX1, and intact ETV6. We identify aberrant enhancer-like activation of GGAA tandem repeats as a characteristic feature of B-cell acute lymphoblastic leukemia (B-ALL) with genetic defects of the ETV6 transcriptional repressor, including ETV6-RUNX1+ and ETV6-null B-ALL. We show that GGAA repeat enhancers are direct activators of previously identified ETV6-RUNX1+ B-ALL “signature” genes, including likely oncogenic drivers. When restored to ETV6-deficient B-ALL cells, ETV6 directly binds to GGAA repeat enhancers, represses their acetylation, downregulates adjacent genes, and inhibits B-ALL growth. In ETV6-deficient B-ALL cells, we find that the ETS transcription factor ERG directly binds to GGAA microsatellite enhancers and is required for sustained activation of many repeat enhancer-activated genes. Together, our findings reveal a novel epigenetic gatekeeper function of the ETV6 tumor suppressor gene and establish microsatellite enhancers as a key mechanism underlying the unique gene expression program of ETV6-RUNX1+ B-ALL.
2022-10-23 | GSE186936 | GEO