Macgoren-Abnornal karyotype
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9583 | GEO | 2008/10/01
SECONDARY ACCESSION(S): PRJNA103417
REPOSITORIES: GEO
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Project description:Human embryonic stem (ES) cell lines acquire recurrent karyotypic abnormalities that may promote growth and survival in long-term culture. Cells with these abnormalities are often present at low levels in human ES cell cultures, requiring subcloning for isolation and analyses. We have developed a rapid method to isolate either abnormal or normal clones from karyotypically mosaic human ES cell cultures that we call Genetic Diagnosis at Passage (G-DAP). We have used this technique to isolate three distinct abnormal sublines from H9 human ES cells in continuous culture. These sublines were characterized by G-banding, fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and array comparative genomic hybridization (aCGH). One subline (H9.DT) has, as it’s only abnormality, a duplication of 12p capped by a 5q subtelomere. A related subline (H9.TSF) has an additional copy of the derivative chromosome 12, partial trisomy of 17q, and trisomy 14. The third subline (H9.DE) has an interstitial deletion of 18q as the sole anomaly. Despite these karyotypic abnormalities, all three sublines retain markers of the undifferentiated state. The subline H9.TSF demonstrated the ability to form embryoid bodies consisting of all three germ layers. Significantly, H9.DT and H9.TSF sublines show a classic karyotype progression that mirrors that seen in both hematopoietic and solid tumors. This progression was accompanied by an impressive increase in growth potential. The isolation of human ES cell sublines with clonal cytogenetic abnormalities provides a valuable tool for study of factors that promote in vitro genetic changes and for analysis of mechanisms of aneuploidy related to genetic progression found in human cancers.
2008-07-18 | GSE12119 | GEO
Project description:Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is the trisomy of chromosome 12. Interestingly, trisomy 12 is also prevalent in germ cell tumors (GCTs). Here, we aimed to dissect the cellular and molecular implications of trisomy 12 in hPSCs. A genome-wide gene expression analysis revealed that trisomy 12 profoundly affects the global gene expression profile of hPSCs, inducing a transcriptional program very similar to that of CGTs. Direct comparison of the proliferation, replication, differentiation and apoptosis between diploid and aneuploid hPSCs revealed that trisomy 12 significantly increases the proliferation rate of hPSCs. Increased replication largely accounts for the increased proliferation observed, and may explain the selection advantage that trisomy 12 confers to hPSCs. A comparison of the tumors induced by diploid and aneuploid hPSCs further demonstrated that trisomy 12 increases the tumorigenicity of hPSCs, inducing transcriptionally-distinct teratomas, from which pluripotent cells can be recovered. Lastly, a chemical screen of 89 anticancer drugs against diploid and aneuploid hPSCs discovered that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors, suggesting that the increased proliferation and tumorigenicity of these aberrant cells also makes them more vulnerable, and might potentially be used for their selective elimination from culture. Together, our findings demonstrate the extensive effect of trisomy 12 on the gene expression signature and on the cellular behavior of hPSCs, and highlight the danger posed by this trisomy for the successful use of hPSCs in basic research and in regenerative medicine.
2014-09-01 | GSE51455 | GEO
Project description:Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Normal cytogenetics (CN) constitutes the single largest group, while trisomy 8 (+8) as a sole abnormality is the most frequent trisomy. How trisomy contributes to tumorigenesis is unknown. We used oligonucleotide-based DNA microarrays to study global gene expression in AML+8 patients with +8 as the sole chromosomal abnormality and AML-CN patients. CD34+ cells purified from normal bone marrow (BM) were also analyzed as a representative heterogeneous population of stem and progenitor cells. Expression patterns of AML patients were clearly distinct from those of CD34+ cells of normal individuals. We show that AML+8 blasts overexpress genes on chromosome 8, estimated at 32% on average, suggesting gene-dosage effects underlying AML+8. Systematic analysis by cellular function indicated up-regulation of genes involved in cell adhesion in both groups of AML compared with CD34+ blasts from normal individuals. Perhaps most interestingly, apoptosis-regulating genes were significantly down-regulated in AML+8 compared with AML-CN. We conclude that the clinical and cytogenetic heterogeneity of AML is due to fundamental biological differences. **NOTE: Migrated from caArray 1.x, identifier='gov.nih.nci.ncicb.caarray:Experiment:1015897559579654:1'
2015-06-26 | GSE70284 | GEO
Project description:Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Normal cytogenetics (CN) constitutes the single largest group, while trisomy 8 (+8) as a sole abnormality is the most frequent trisomy. How trisomy contributes to tumorigenesis is unknown. We used oligonucleotide-based DNA microarrays to study global gene expression in AML+8 patients with +8 as the sole chromosomal abnormality and AML-CN patients. CD34+ cells purified from normal bone marrow (BM) were also analyzed as a representative heterogeneous population of stem and progenitor cells. Expression patterns of AML patients were clearly distinct from those of CD34+ cells of normal individuals. We show that AML+8 blasts overexpress genes on chromosome 8, estimated at 32% on average, suggesting gene-dosage effects underlying AML+8. Systematic analysis by cellular function indicated up-regulation of genes involved in cell adhesion in both groups of AML compared with CD34+ blasts from normal individuals. Perhaps most interestingly, apoptosis-regulating genes were significantly down-regulated in AML+8 compared with AML-CN. We conclude that the clinical and cytogenetic heterogeneity of AML is due to fundamental biological differences. **NOTE: Migrated from caArray 1.x, identifier='gov.nih.nci.ncicb.caarray:Experiment:1015897559579654:1' krahe-00060 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Tissue Sites: Bone marrow Material Types: synthetic_DNA, synthetic_RNA, organism_part Cell Types: Myeloid Cell Disease States: Acute Myeloid Leukemia, Normal
2015-06-26 | E-GEOD-70284 | biostudies-arrayexpress
Project description:Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is the trisomy of chromosome 12. Interestingly, trisomy 12 is also prevalent in germ cell tumors (GCTs). Here, we aimed to dissect the cellular and molecular implications of trisomy 12 in hPSCs. A genome-wide gene expression analysis revealed that trisomy 12 profoundly affects the global gene expression profile of hPSCs, inducing a transcriptional program very similar to that of CGTs. Direct comparison of the proliferation, replication, differentiation and apoptosis between diploid and aneuploid hPSCs revealed that trisomy 12 significantly increases the proliferation rate of hPSCs. Increased replication largely accounts for the increased proliferation observed, and may explain the selection advantage that trisomy 12 confers to hPSCs. A comparison of the tumors induced by diploid and aneuploid hPSCs further demonstrated that trisomy 12 increases the tumorigenicity of hPSCs, inducing transcriptionally-distinct teratomas, from which pluripotent cells can be recovered. Lastly, a chemical screen of 89 anticancer drugs against diploid and aneuploid hPSCs discovered that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors, suggesting that the increased proliferation and tumorigenicity of these aberrant cells also makes them more vulnerable, and might potentially be used for their selective elimination from culture. Together, our findings demonstrate the extensive effect of trisomy 12 on the gene expression signature and on the cellular behavior of hPSCs, and highlight the danger posed by this trisomy for the successful use of hPSCs in basic research and in regenerative medicine. Expression data from diploid and aneuoploid human pluripotent stem cells, teratomas derived from them, and pluripotent-like cells recovered from these teratomas total RNA was isolated from undifferentiated human pluripotent stem cells grown under standard human ES conditions, or from teratomas derived from them, or from ES-like cells recovered from these teratomas.
2014-09-01 | E-GEOD-51455 | biostudies-arrayexpress
Project description:Clinical-grade human embryonic stem cells (hESCs) from 4 centres in the UK were cultured in self-renewal conditions Genomic DNA was isolated from low passage hESCs and submitted for SNP analysis using Illumina HumanCytoSNP-12 v2.1 BeadChip arrays
2015-05-05 | GSE68508 | GEO
Project description:Trisomy of chromosome 21, the genetic cause of Down syndrome, has the potential to alter expression of genes on chromosome 21, as well as other locations throughout the genome. These transcriptome changes are likely to underlie the Down syndrome clinical phenotypes. We have employed RNA-seq to undertake an in-depth analysis of transcriptome changes resulting from trisomy of chromosome 21, using induced pluripotent stem cells (iPSCs) derived from a single individual with Down syndrome. These cells were originally derived by Li et al, who genetically targeted chromosome 21 in trisomic iPSCs, allowing selection of disomic sibling iPSC clones. Analyses were conducted on trisomic/disomic cell pairs maintained as iPSCs or differentiated into cortical neuronal cultures.
2018-04-09 | GSE101942 | GEO
Project description:Down syndrome is a common disorder with enormous medical and social costs, caused by trisomy for Chr21. We tested the concept that gene imbalance across an extra chromosome can be de facto corrected in DS patient stem cells by manipulating a single gene, XIST. Using zinc finger nucleases, we targeted a large, inducible XIST transgene into the Chr21 DYRK1A locus, in DS pluripotent stem cells. XIST RNA coats Chr21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a “Chr21 Barr Body.” This provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise. In this study, we used microarrays to understand the genome-wide impacts of inducible XIST expression on Chr21 in trisomy 21 human iPS cell lines, and to evaluate the extent of Chr21 silencing trisomic samples versus a disomic male iPS cell line.
2013-07-12 | GSE47014 | GEO
Project description:Induced pluripotent stem cells (iPSCs) from patients are an attractive disease model to study tissues with poor accessibility such as the brain. Using this approach, we and others have shown that trisomy 21 results in genome-wide transcriptional dysregulations. The effects of loss of genes on chromosome 21 is much less characterized. Here, we use patient-derived neural cells from an individual with neurodevelopmental delay and a ring chromosome 21 with two deletions spanning 3.8 Mb at the terminal end of 21q22.3, containing 60 protein-coding genes. To investigate the molecular perturbations of the partial monosomy on neural cells, we established patient-derived iPSCs from fibroblasts retaining the ring chromosome 21, and we then induced iPSCs into neuroepithelial stem cells (NESCs). RNA-Seq analysis of NESCs with the ring chromosome revealed downregulation of 18 genes within the deleted region together with global transcriptomic dysregulations when compared to euploid NESCs. Since the deletions on chromosome 21 represent a genetic “contrary” to trisomy of the corresponding region, we further compared the dysregulated transcriptomic profile in with that of two NESC lines with trisomy 21. The analysis revealed opposed expression changes for 23 genes on chromosome 21 as well as 149 non-chromosome 21 genes. Taken together, our results bring insights into the effects on the global and chromosome 21 specific gene expression from a partial monosomy of chromosome 21qter during early neuronal differentiation.
2022-01-09 | GSE190053 | GEO
Project description:Multiple myeloma is a relatively common B-cell malignancy that is currently incurable. Certain recurrent genetic abnormalities characteristics of different genetic subtypes have been described. Hyperdiploid myeloma characterized by recurrent trisomies is the most common genetic subtypes. However little is know about it's biology. Another common genetic abnormality is chromosome 13 deletion which is also associated with inferior prognosis. This abnormality is already present at the pre-malignant MGUS stage and is clonally selected with disease progression. Although it is biologically and clinically important the molecular consequence of chromosome 13 deletion is unknown. Keywords: disease subtype analysis
2007-04-01 | GSE6477 | GEO