Parallel SNP and CGH arrays of cytogenetic normal MDS patients and detection of alterations present in CD3+ T cells and bone marrow cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE49004 | GEO | 2017/01/01
SECONDARY ACCESSION(S): PRJNA212571
REPOSITORIES: GEO
Similar Datasets
Project description:Clonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed. The study included data on 1007 patients, 1-75 years old (median 45 years), transplanted from related (n = 547) or unrelated (n = 460) donors. Various conditioning regimens were used, and marrow, peripheral blood, or cord blood served as stem cell source. Both IPSS and 5-group cytogenetic risk classifications were significantly associated with post-HCT relapse and mortality, but the 5-group classification discriminated more clearly among the lowest- and highest-risk patients. A monosomal karyotype tended to further increase the rates of relapse and mortality, even after considering the IPSS or 5-group classifications. In addition, the pathologic disease category correlated with both relapse and mortality. Mortality was also impacted by patient age, donor type, conditioning regimen, platelet count, and etiology of MDS. Although mortality declined significantly in recent years, novel strategies are needed to overcome the barrier of high-risk cytogenetics.
| S-EPMC3478516 | biostudies-literature
Project description:Purpose: The purpose of this study was to evaluate SNP genotyping methodology as a means to detect chromosomal abnormalities previously diagnosed by G-band karyotype or fluorescence in situ hybridization (FISH) analysis and to determine the frequency of sub-microscopic (cryptic) chromosomal alterations in these subjects. Methods: We used the Illumina HumanHap Beadchip platform to genotype 40 individuals having previously detected chromosomal anomalies (by G-banded and/or FISH analysis). The resulting data were analyzed for signal intensity (log R ratio) and allelic composition (B allele frequency). Results: SNP array analysis detected 100% of previously identified cytogenetic abnormalities. Changes or clarifications of the ISCN karyotype designation assigned by conventional cytogenetic and/or FISH analysis were made in 82 % of the cases (32 of 39). Nine of the 39 cases (23%) involved a reassignment of an abnormal band while an additional 9 of the 39 (23%) resulted in a clarification of a sub-band assignment. In 8 more of the 39 cases (21%) the previously reported alterations were confirmed, however the SNP analysis also identified related cryptic alterations. SNP analysis not only confirmed FISH-detected abnormalities but also more precisely mapped the breakpoints of 6/6 patients. Investigations into the origin of de novo abnormalities in 15 trio families established that 12 /15 occurred on the paternal chromosome. Conclusions: SNP genotyping array analysis, confirmed all previously detected structural chromosomal abnormalities and provided additional, clinically-relevant genomic information in 82% of these alterations.
2011-02-22 | GSE20623 | GEO
Project description:Early, low risk IPSS (International Prognostic Scoring System) myelodysplasia (MDS) is a heterogeneous disorder where the molecular and cellular haematopoietic defects are poorly understood. To gain insight into this condition, we analyzed gene expression profiles of marrow CD34+ progenitor cells from normal karyotype, low blast count MDS patients, age-matched controls and patients with non-MDS anaemia. The aim of the study was to further understanding of the cellular defect in MDS and to identify biomarkers of disease Keywords: Disease v normal
2005-08-05 | GSE2779 | GEO
Project description:Parallel aSNP and aCGH analyses were performed on 22 samples from MDS patients with a normal karyotype. 55 overlapping alterations, most of these corresponding to CNVs were identified with both methods. Putative tumour specific imbalances were found with both methods in three cases, a deletion of TET2, a larger deletion containing DNMT3A and one complex molecular karyotype. In two cases putative tumour specific imbalances were only seen with aCGH: a 16p deletion in a low number of cells and a small homozygous deletion in WWOX. Telomeric UPDs were only detected with aSNP in two cases: one affecting chromosome 3q and in the other, two UPD regions were present on 4q and 5p. In total, putative relevant tumour specific genomic alterations were found in seven cases (32%). Three small aberrations only detected by aCGH were present in T-cells, suggestive of germ line alterations which may confer a risk for MDS development. This part contains the aCGH analyses, for aSNP see GSE49004.
2017-01-01 | GSE50897 | GEO
Project description:Purpose: The purpose of this study was to evaluate SNP genotyping methodology as a means to detect chromosomal abnormalities previously diagnosed by G-band karyotype or fluorescence in situ hybridization (FISH) analysis and to determine the frequency of sub-microscopic (cryptic) chromosomal alterations in these subjects. Methods: We used the Illumina HumanHap Beadchip platform to genotype 40 individuals having previously detected chromosomal anomalies (by G-banded and/or FISH analysis). The resulting data were analyzed for signal intensity (log R ratio) and allelic composition (B allele frequency). Results: SNP array analysis detected 100% of previously identified cytogenetic abnormalities. Changes or clarifications of the ISCN karyotype designation assigned by conventional cytogenetic and/or FISH analysis were made in 82 % of the cases (32 of 39). Nine of the 39 cases (23%) involved a reassignment of an abnormal band while an additional 9 of the 39 (23%) resulted in a clarification of a sub-band assignment. In 8 more of the 39 cases (21%) the previously reported alterations were confirmed, however the SNP analysis also identified related cryptic alterations. SNP analysis not only confirmed FISH-detected abnormalities but also more precisely mapped the breakpoints of 6/6 patients. Investigations into the origin of de novo abnormalities in 15 trio families established that 12 /15 occurred on the paternal chromosome. Conclusions: SNP genotyping array analysis, confirmed all previously detected structural chromosomal abnormalities and provided additional, clinically-relevant genomic information in 82% of these alterations. To evaluate potential chromosomal abnormalities in patients, we measured SNPs using Illumina 550K and 300K arrays. In some cases we also measured SNPs in parents to determine whether deletions or duplications occurred de novo or were inherited.
2011-02-22 | E-GEOD-20623 | biostudies-arrayexpress
Project description: Not available
| S-EPMC9440217 | biostudies-literature
Project description:Clonal cytogenetic evolution (CE) (i.e., acquisition of new chromosomal aberrations over time) is relevant for the progression of myelodysplastic syndromes (MDS). We performed detailed analysis of CE in 729 patients with MDS and related disorders. Patients with CE showed shorter survival (median OS 18.0 versus 53.9 months; P?<?0.01), higher leukemic transformation rate (48.0% versus 21.4%; P?<?0.01) and shorter intervals to leukemic transformation (P?<?0.01). Two main CE patterns were detected: early versus late CE (median onset 5.3 versus 21.9 months; P?<?0.01) with worse survival outcomes for early CE. In the case of CE, del (7q)/-7 (P?=?0.020) and del (17p) (P?=?0.002) were especially unfavorable. Extending the evolution patterns from Tricot et al. (1985) forming five subgroups, prognosis was best (median OS not reached) in patients with "transient clones/changing clone size", whereas those with "CE at diagnosis" showed very poor outcomes (P?<?0.01 for comparison of all). Detailed sequential cytogenetic analysis during follow-up improves prognostication in MDS patients and acknowledges the dynamic biology of the disease. Evidence, time-point, and patterns of cytogenetic clonal evolution should be included into future prognostic scoring systems for MDS.
| S-EPMC5841340 | biostudies-literature
Project description:AML/MDS patients carrying 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are characterized by a complex aberrant karyotype (CAK) frequently including deletions within 5q, 17p and 7q, a later onset and fast progression of the disease with extremely poor prognosis. We and others have shown that the MLL gene is overexpressed in amplified cases; however, in most of the cases the amplified region is not restricted to the MLL locus. In the present study we investigated 19 patients with AML/MDS and MLL gain/amplification. By means of array CGH performed in 12 patients we were able to delineate the minimal deleted regions within 5q, 17p and 7q and identified three independent regions 11q/I-III that were amplified in all cases. Gene expression profiles established in 15 cases (GSE10258) were used to define candidate genes within these regions. Interestingly, analysis of our data suggests an interdependency of loss of 5q and 17p and expression of genes present in 11q23-25. Furthermore, we demonstrate that the gene expression signature can be used to discriminate AML/MDS with MLL amplification from several other types of AML, thus, indicating specific pathogenesis present in this entity. Keywords: comparative genomic hybridization; array CGH
2008-07-01 | GSE9928 | GEO
Project description:Full Title: Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: A comparison of 408 cases classified as “AML not otherwise specified” or “AML with myelodysplasia-related changes” The WHO classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetic information, data on patients’ history, and multilineage dysplasia (MLD). The category “AML with MDS-related changes” (AML-MRC) is separated from AML not otherwise specified (AML-NOS) by the presence of either MLD, MDS-related cytogenetics or MDS history. To clarify whether MLD alone is clinically relevant, we analyzed 408 adult patients categorized as AML-MRC or AML-NOS. EFS (Median 13.8 months vs. 16.0 months) and 3-year-OS (45.8% vs. 53.9%) did not differ significantly between patients with MLD and without. However, MLD correlated with pre-existing MDS (p<0.001) and MDS-related cytogenetics (p=0.035). Patients with MLD as sole AML-MRC criterion (AML-MLD-sole; n=90) had less frequently FLT3-ITD (p=0.032), and a lower median age than AML-NOS (n=232), but EFS, OS, and WBC did not differ significantly. Contrarily, patients with AML-NOS plus AML-MLD-sole (n=323) versus patients with MDS history or MDS-related cytogenetics (n=85) had better EFS (16.9 vs. 10.7 months; p=0.005) and 3-year-OS (55.8% vs. 32.5%; p=0.001). Gene expression profiles were measured for a subset of 96 patients. Analysis of the expression data showed distinct clusters for AML-MLD-sole and AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD demonstrated no independent clinical impact, while cytogenetics and MDS history were of prognostic relevance. This data suggest modifications in a revised WHO proposal.
2011-01-01 | GSE21261 | GEO
Project description:AML/MDS patients carrying 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are characterized by a complex aberrant karyotype (CAK) frequently including deletions within 5q, 17p and 7q, a later onset and fast progression of the disease with extremely poor prognosis. We and others have shown that the MLL gene is overexpressed in amplified cases; however, in most of the cases the amplified region is not restricted to the MLL locus. In the present study we investigated 19 patients with AML/MDS and MLL gain/amplification. By means of array CGH performed in 12 patients we were able to delineate the minimal deleted regions within 5q, 17p and 7q and identified three independent regions 11q/I-III that were amplified in all cases. Gene expression profiles established in 15 cases (GSE10258) were used to define candidate genes within these regions. Interestingly, analysis of our data suggests an interdependency of loss of 5q and 17p and expression of genes present in 11q23-25. Furthermore, we demonstrate that the gene expression signature can be used to discriminate AML/MDS with MLL amplification from several other types of AML, thus, indicating specific pathogenesis present in this entity. Keywords: comparative genomic hybridization; array CGH In this study, aCGH analysis performed on 12 DNA samples derived from patients with AML, preselected for the presence of MLL amplifications, were analysed on a submegabase resolution BAC array. No replicates, no dye swap was done. Gene expression profiling performed for 15 AML patients (GSE10258).
2008-06-30 | E-GEOD-9928 | biostudies-arrayexpress