Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA362665 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Metaphase karyotyping is an established diagnostic standard in acute myeloid leukemia (AML) for risk stratification. One of the cytogenetic findings in AML are structurally highly abnormal marker chromosomes. In this study, we have assessed frequency, cytogenetic characteristics, prognostic impact and underlying biological origin of marker chromosomes. Given their inherent gross structural chromosomal damage, we speculated that they may arise from chromothripsis, a recently described phenomenon of chromosome fragmentation in a single catastrophic event. In 2 large consecutive prospective, randomized, multicenter, intensive chemotherapy trials (AML96, AML2003) from the Study Alliance Leukemia (SAL), marker chromosomes were detectable in 165/1026 (16.1%) of aberrant non-core-binding-factor (CBF) karyotype patients. Adverse-risk karyotypes displayed a higher frequency of marker chromosomes (26.5% in adverse-risk, 40.3% in complex aberrant and 41.2% in abnormality(17p) karyotypes, p<.0001 each). Marker chromosomes were associated with a poorer prognosis compared to other non-CBF aberrant karyotypes and led to lower remission rates (CR+CRi), inferior event-free survival as well as overall survival in both trials. In multivariate analysis, marker chromosomes independently predicted poor prognosis in the AML96 trial ≤60 years. As detected by array-CGH, about one third of marker chromosomes (18/49) had arisen from chromothripsis, whereas this phenomenon was virtually undetectable in a control group of marker chromosome-negative complex aberrant karyotypes (1/34). The chromothripsis-positive cases were characterized by a particularly high degree of karyotype complexity and dismal prognosis. In conclusion, marker chromosomes are indicative of chromothripsis and associated with poor prognosis per se and not merely by association with other adverse cytogenetic features.
2017-03-29 | GSE93886 | GEO
Project description:Acute myeloid leukemia (AML) patients carrying complex karyotype or aneuploidies have a very poor prognosis, with a 5-year overall survival lower than 20%. We and others have shown that complex karyotype and aneuploid patients are characterized by high genomic instability, along with defects of DNA damage response genes and, occasionally, by chromothripsis. Chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology. Moreover, the homology recombination pathway is frequently deregulated at expression level in AML. We showed that PALB2 is affect by copy-number deletions in AML (5.2%) and it may be a potential biomarker for very-poor prognosis AML.
2021-01-19 | GSE160982 | GEO
Project description:Loss of chromosome 7 and del(7q) [-7/del(7q)] are recurring cytogenetic abnormalities in hematologic malignancies, including acute myeloid leukemia and therapy-related myeloid neoplasms, and associated with an adverse prognosis. We performed SNP array analysis on de novo and therapy-related myeloid neoplasms and identified a 2.17 Mb commonly deleted segment on chromosome band 7q22.1 containing CUX1, a gene encoding a homeodomain-containing transcription factor. Haploinsufficiency of the highly conserved ortholog, cut, led to hemocyte overgrowth and tumor formation in Drosophila melanogaster. Similarly, haploinsufficiency of CUX1 gave human hematopoietic cells a significant engraftment advantage upon transplantation into immunodeficient mice. These data identify CUX1 as a conserved, haploinsufficient tumor suppressor frequently deleted in myeloid neoplasms. We performed SNP-array analysis of 34 primary patient samples with de novo or therapy-related myeloid leukemia and one acute myeloid leukemia cell line, UoCM1. For patient samples, DNA was obtained from the white blood cells of bone marrow or peripheral blood leukemia specimens. Cytogenetic analysis revealed clonal -7/del(7q) in 17 of the cases.
2012-11-24 | E-GEOD-42482 | biostudies-arrayexpress
Project description:This dataset contains data from two acute myeloid leukaemia (AML) specimens processed with the Illumina CytoSNP-12 SNP array platform. SNP array data showed evidence of chromothripsis in these two specimens. Each deletion in the mosaic specimen was present in the same proportion of cells, which supports the view that the many breaks occur as a single event. Complementary FISH studies highlighted the inclusion of centromeres from different chromosomes during the formation of the new chromosomes. Residual bone marrow specimens were chosen from patients who were determined to have a complex karyotype which included abnormalities of chromosomes 5 and 17, by routine cytogenetic examination.
2013-08-04 | E-GEOD-43522 | biostudies-arrayexpress
Project description:This dataset contains data from two acute myeloid leukaemia (AML) specimens processed with the Illumina CytoSNP-12 SNP array platform. SNP array data showed evidence of chromothripsis in these two specimens. Each deletion in the mosaic specimen was present in the same proportion of cells, which supports the view that the many breaks occur as a single event. Complementary FISH studies highlighted the inclusion of centromeres from different chromosomes during the formation of the new chromosomes.
2013-08-04 | GSE43522 | GEO
Project description:MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia
2008-01-10 | E-TABM-405 | biostudies-arrayexpress
Project description:RUNX family transcription factor 1 (RUNX1) mutated acute myeloid leukemia (AML) has now been formally classified as AML with myelodysplasia-related gene mutations, and considered to predict adverse prognosis. In addition, mutations of RUNX1 and plant homeodomain finger gene 6 (PHF6) frequently co-occurred and conferred particularly adverse clinical outcomes. Becasue the pathological effects of these combined mutations remained understudied, we sought to address this topic through genetically modified mouse models. We found that Phf6 knockout and RUNX1 double-mutated bone marrow (BM) cells displayed significantly higher engraftment capacity, and recipient mice transplanted with double-mutated BM cells developed AML with significantly shortened survival. We also discovered that the multipotent progenitors (MPPs) were the main cell subpopulation responsible for double-mutated BM cell-induced leukemia. Our findings highlighted the synergistic leukemogenic potential of Phf6 and RUNX1 mutations in vivo, and provided evidence for possible underlying molecular mechanisms.
2025-08-06 | GSE275754 | GEO
Project description:Genomic rearrangements typically occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving chromosome shattering and reshuffling ('chromothripsis'), for which no genetic basis has yet been described. Whole-genome sequencing of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome) revealed massive, complex rearrangements resulting from chromothripsis. Integrating TP53 status with genomic rearrangement data in additional medulloblastomas revealed a striking association between TP53 mutation and chromothripsis in SHH-MBs. Unexpectedly, five seemingly sporadic SHH-MB patients with chromothripsis harbored TP53 germline mutations – findings relevant for clinical management. Analysis of additional tumor entities substantiated a link between TP53 mutation and chromothripsis, beyond general genomic instability. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings implicate p53 in the initiation of, or cellular reaction to, chromothripsis – a novel role for the 'guardian of the genome'.
2012-01-20 | GSE34258 | GEO
Project description:Genomic rearrangements typically occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving chromosome shattering and reshuffling ('chromothripsis'), for which no genetic basis has yet been described. Whole-genome sequencing of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome) revealed massive, complex rearrangements resulting from chromothripsis. Integrating TP53 status with genomic rearrangement data in additional medulloblastomas revealed a striking association between TP53 mutation and chromothripsis in SHH-MBs. Unexpectedly, five seemingly sporadic SHH-MB patients with chromothripsis harbored TP53 germline mutations – findings relevant for clinical management. Analysis of additional tumor entities substantiated a link between TP53 mutation and chromothripsis, beyond general genomic instability. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings implicate p53 in the initiation of, or cellular reaction to, chromothripsis – a novel role for the 'guardian of the genome'. The DNA copy-number profiles of 11 primary medulloblastoma samples were analyzed on the Affymetrix Mapping250K Nsp array, together with data from 70 primary samples taken from GSE21140. Data from diploid reference samples were taken from GSE9222. Additionally, DNA copy-number profiles for 19 additional medulloblastoma samples were generated on the Affymetrix SNP6 platform with matched blood samples.
2012-01-20 | E-GEOD-34258 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) is a heterogeneous disease in respect of molecular aberrations and prognosis. We used gene expression profiling of 562 patients treated in the German AMLCG 1999 trial to develop a gene signature that predicts survival in AML. Analysis of 562 samples (140 HGU-133plus2; 422 HGU-133A; 422 HGU-133B) from adult patients with acute myeloid leukemia (AML).
2013-02-07 | E-GEOD-37642 | biostudies-arrayexpress