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Detection of chromothripsis-like patterns from custom array platform for chronic lymphocytic leukemia diagnosis (qchip Hemo custom array v3)

ABSTRACT: Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. The main genetic alterations associated to this disease are loss of 13q14, loss of 11q23, trisomy 12 and, less frequently, 17p13 losses, and are routinely studied using fluorescence in situ hybridization. These genomic aberrations have been demonstrated to be important independent predictors of disease progression in CLL and their detection currently has a direct implication in the treatment strategy of the patients. It has been widely demonstrated that array-based karyotyping clearly detects DNA gains and losses and allows the identification of CLL abnormalities not included in the standard FISH panel. We have here established and tested an oligonucleotide-based array platform for the diagnosis of CLL that interrogates the most relevant chromosomal regions related with the disease and may help in the differential diagnosis between CLL and other small B-cell leukemias and may be used as a powerful prognosis tool to stratify the CLL patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66922 | GEO | 2015/08/31

SECONDARY ACCESSION(S): PRJNA278374

REPOSITORIES: GEO

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Detection of chromothripsis-like patterns from custom array platform for chronic lymphocytic leukemia diagnosis (qchip Hemo custom array v3)

Project description:Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries. The main genetic alterations associated to this disease are loss of 13q14, loss of 11q23, trisomy 12 and, less frequently, 17p13 losses, and are routinely studied using fluorescence in situ hybridization. These genomic aberrations have been demonstrated to be important independent predictors of disease progression in CLL and their detection currently has a direct implication in the treatment strategy of the patients. It has been widely demonstrated that array-based karyotyping clearly detects DNA gains and losses and allows the identification of CLL abnormalities not included in the standard FISH panel. We have here established and tested an oligonucleotide-based array platform for the diagnosis of CLL that interrogates the most relevant chromosomal regions related with the disease and may help in the differential diagnosis between CLL and other small B-cell leukemias and may be used as a powerful prognosis tool to stratify the CLL patients. Copy number analysis using Custom Agilent 60K was performed on 47 chronic lymphocytic Leukemia patients with sex-matched control DNAs

2015-08-31 | E-GEOD-66922 | biostudies-arrayexpress

Detection of chromothripsis-like patterns from custom array platform for chronic lymphocytic leukemia diagnosis (qchip Hemo custom array v1)

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Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia – unexpected expression pattern of the RHO GTPase activator ARHGAP20

Project description:In chronic lymphocytic leukemia (CLL), 13q14 and 11q22-23 deletions are found in 2/3 of the cases. 11q22-23 deletions are associated with poor survival, whereas 13q14 deletions as single abnormality are often found in indolent disease forms. The molecular basis for this difference in prognosis is not known. ARHGAP20 encodes an evolutionarily conserved protein. In the zebra fish (Danio rerio) genome the syntenic regions of human chromosomal bands 13q14 and 11q22-23 are juxtaposed. The similar expression profiles of ARHGAP20 in 13q14 and 11q22-23 deleted CLL cases suggest a molecular connection and an intriguing mechanism of regulation.

2011-10-14 | GSE25571 | GEO

Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia – unexpected expression pattern of the RHO GTPase activator ARHGAP20

2011-10-13 | E-GEOD-25571 | biostudies-arrayexpress

Detection of chromothripsis-like patterns with a custom array platform for chronic lymphocytic leukemia.

Project description:Chronic lymphocytic leukemia (CLL) is a common disease with highly variable clinical course. Several recurrent chromosomal alterations are associated with prognosis and may guide risk-adapted therapy. We have developed a targeted genome-wide array to provide a robust tool for ascertaining abnormalities in CLL and to overcome limitations of the 4-marker fluorescence in situ hybridization (FISH). DNA from 180 CLL patients were hybridized to the qChip®Hemo array with a high density of probes covering commonly altered loci in CLL (11q22-q23, 13q14, and 17p13), nine focal regions (2p15-p16.1, 2p24.3, 2q13, 2q36.3-q37.1, 3p21.31, 8q24.21, 9p21.3, 10q24.32, and 18q21.32-q21.33) and two larger regions (6q14.1-q22.31 and 7q31.33-q33). Overall, 86% of the cases presented copy number alterations (CNA) by array. There was a high concordance of array findings with FISH (84% sensitivity, 100% specificity); all discrepancies corresponded to subclonal alterations detected only by FISH. A chromothripsis-like pattern was detected in eight cases. Three showed concomitant shattered 5p with gain of TERT along with isochromosome 17q. Presence of 11q loss was associated with shorter time to first treatment (P = 0.003), whereas 17p loss, increased genomic complexity, and chromothripsis were associated with shorter overall survival (P < 0.001, P = 0.001, and P = 0.02, respectively). In conclusion, we have validated a targeted array for the diagnosis of CLL that accurately detects, in a single experiment, all relevant CNAs, genomic complexity, chromothripsis, copy number neutral loss of heterozygosity, and CNAs not covered by the FISH panel. This test may be used as a practical tool to stratify CLL patients for routine diagnostics or clinical trials.

| S-EPMC4832286 | biostudies-literature

Comparative genomic hybridization of human chronic lymphocytic leukemia samples with a small 13q14 deletion and normal genomic DNA.

Project description:It has been widely recognized that a 13q14 deletion is often found in CLL and that this deletion is associated with a good prognosis. Such deletions are sometime detected only by fluorescence in situ hybridization (FISH) [1] because they are too small to be detected by banding. We report here a small deletion that is undetectable by FISH but identifiable by high-resolution comparative genomic hybridization (CGH) arrays. A 62-year-old patient with previously untreated chronic lymphocytic leukemia (CLL; BinetÕs stage A) was studied because of a recent increase of his lymphocyte counts. The patient had been in stage A since the initial diagnosis was made 12 years before. At the time of cytogenetic analysis, the peripheral lymphocyte count was 65.3 g/L with weak llight chain surface imunoglobulin expression and a Matutes score of 5/5. The karyotype of 12-O-tetradecanoylphorbal 13-acetate-stimulated blood cells was 46,X,-Y[3]/46,XY [17]. FISH with X and Y probes confirmed that 90% of the blood cells had a Y chromosome loss, which is an infrequent but recurrent finding in CLL. FISH of 200 cells found no 13q14 deletion.

2008-06-09 | E-TABM-293 | biostudies-arrayexpress

Array comparative genomic hybridization data from 313 CLL specimens to study outcome associations

Project description:This study investigates genomic imbalance in chronic lymphocytic leukemia (CLL) and aims to identify genomic gains and losses with prognostic significance.

2013-09-07 | GSE40834 | GEO

Transcription profiling of genetically and clinically distinct subgroups of human B-cell chronic lymphocytic leukemia patients

Project description:We used high density oligonucleotide arrays to identify molecular correlates of genetically and clinically distinct subgroups of B-cell chronic lymphocytic leukemia (B-CLL). Gene expression profiling was used to profile the five most frequent genomic aberrations, namely deletions affecting chromosome bands 13q14, 11q22-q23, 17p13 and 6q21, and gains of genomic material affecting chromosome band 12q13. A strikingly high degree of correlation between loss or gain of genomic material and the amount of transcripts from the affected regions leads to the hypothesis of gene dosage as a significant pathogenic factor. Furthermore, the influence of the immunoglobulin variable heavy chain (VH) mutation status was determined. A clear distinction in the expression profiles of unmutated and mutated VH samples exists, which can be discovered using unsupervised learning methods. However, when samples were separated by gender, this separation could only be detected in samples from male patients. Since the samples were either hybridized onto HG-U95A arrays or onto HG-U95Av2 arrays, only genes common to both arrays were used for further analysis. This study is described in more detail in Haslinger C, et al. 2004. J Clin Oncol. 22:3937-3949; Series _keyword: CLL, chronic lymphocytic leukemia, immunoglobulin somatic hypermutation, genomic aberrations

2007-08-25 | E-GEOD-2466 | biostudies-arrayexpress

Array comparative genomic hybridization data from 313 CLL specimens to study outcome associations

Project description:This study investigates genomic imbalance in chronic lymphocytic leukemia (CLL) and aims to identify genomic gains and losses with prognostic significance. Two-condition experiment, Test CLL specimens vs. Reference human genome DNA equimixture of normal male and normal female.

2013-09-07 | E-GEOD-40834 | biostudies-arrayexpress

B_Cell_Chronic_Lymphocytic_Leukemia

Project description:We used high density oligonucleotide arrays to identify molecular correlates of genetically and clinically distinct subgroups of B-cell chronic lymphocytic leukemia (B-CLL). Gene expression profiling was used to profile the five most frequent genomic aberrations, namely deletions affecting chromosome bands 13q14, 11q22-q23, 17p13 and 6q21, and gains of genomic material affecting chromosome band 12q13. A strikingly high degree of correlation between loss or gain of genomic material and the amount of transcripts from the affected regions leads to the hypothesis of gene dosage as a significant pathogenic factor. Furthermore, the influence of the immunoglobulin variable heavy chain (VH) mutation status was determined. A clear distinction in the expression profiles of unmutated and mutated VH samples exists, which can be discovered using unsupervised learning methods. However, when samples were separated by gender, this separation could only be detected in samples from male patients. Since the samples were either hybridized onto HG-U95A arrays or onto HG-U95Av2 arrays, only genes common to both arrays were used for further analysis. This study is described in more detail in Haslinger C, et al. 2004. J Clin Oncol. 22:3937-3949 Series _keyword: CLL, chronic lymphocytic leukemia, immunoglobulin somatic hypermutation, genomic aberrations Keywords: other

2005-04-01 | GSE2466 | GEO

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