Affymetrix SNP array data for cone precursor derived retinoblastoma like samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE60720 | GEO | 2014/08/25
SECONDARY ACCESSION(S): PRJNA259361
REPOSITORIES: GEO
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Project description:Retinoblastoma is a childhood retinal tumor that initiates in response to biallelic RB1 inactivation. We show that post-mitotic human cone precursors are uniquely sensitive to the oncogenic effects of Rb depletion. Rb knockdown induced cone precursor proliferation in prospectively isolated populations. SNP-array analysis of two Rb/p130-depleted cone precursor cell lines, revealing no megabase-size loss of heterozygosity (LOH) or copy number alterations (CNAs). SNP-array analysis of one Rb/p130-depleted (tumor 1) or one Rb-depleted (tumor 2) cone precursor-derived tumors, revealing no megabase-size LOH or CNAs, consistent with the lack of DNA copy number alterations in some retinoblastomas. Thus, the cone precursor tumors resembled human retinoblastomas at the molecular cytogenetic level. High resolution SNP-array DNA copy number analyses were performed using CytoScan® HD (Affymetrix, 901835) according to the manufacturer's directions. Data were analyzed using Chromosome Analysis Suite 2.0 (Affymetrix). DNA was extracted from two Rb/p130 depleted cone precursor cell lines and two cryopreserved mouse retinoblastoma samples from eyes xenograted with Rb/p130 or Rb depleted cone precursors. Affymetrix SNP analysis on retinoblastoma cell lines Y79, RB176, and WERI were used as control. Normal human genome 19 was used as reference.
2014-08-25 | E-GEOD-60720 | biostudies-arrayexpress
Project description:Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested.
2008-12-10 | GSE13557 | GEO
Project description:Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested. 10 chronic lymphocytic leukemia (CLL) samples was analyzed using four different high-resolution platforms: 32K BAC arrays, 185K Agilent oligonucleotide arrays, 250K Affymetrix SNP arrays and 317K Illumina SNP arrays.
2008-12-10 | E-GEOD-13557 | biostudies-arrayexpress
Project description:Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. The diverse malignant and immune cells in tumors determine tumor progression, but the intratumoral heterogeneity, tumor microenvironment and their impact in RB remain poorly characterized. Here, we conducted transcriptomic profiles of around 70,000 cells from tumor samples of seven RB patients with pathological and clinical measurements. Fifteen cell types were identified where the majority were cone precursor-like (CP-like) and MKI67+ cone precursor (MKI67+ CP) cells. These cells expressed markers of cone precursor, suggesting that RB originated from cone precursor cells. The conversion of CP-like to MKI67+ CP led to the loss of photoreceptor function and increased cell proliferation ability in RB. By integrative copy number variation analysis, we found that two subtypes of MKI67+ CP cells were more malignant related to cell proliferation. The tumor microenvironment in RB was composed of three cell types, of which glial cells, including tumor-associated macrophages and astrocytes-like cells, created an immunosuppressive environment and promoted tumor growth and invasion by inhibiting the GALECTIN signaling pathway. Together, our study presents the first transcriptomic map of RB at a single-cell resolution and provides novel insights into the occurrence and progression of RB which will be important to the development of the future targeted therapy and immunotherapy.
2022-05-11 | GSE168434 | GEO
Project description:Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients. Single nucleotide polymorphism (SNP)-arrays allow simultaneous detection of copy-number aberrations (CNAs) and copy-number neutral loss-of-heterozygosity (CNN-LOH). In this study we investigated the presence of CNAs and CNN-LOH in newly diagnosed CLL samples from a Swedish chronic lymphocytic leukemia (CLL) cohort. In this study we could detect the known recurrent aberrations in CLL (i.e. deletions of 13q, 11q, 17p and trisomy 12). We also detected other both large and small CNAs which were mostly non-recurrent. CNN-LOH was detected on chromosome 13q in patients that carried homozygous deletion of 13q.
2009-11-23 | GSE16406 | GEO
Project description:We analysed, by last-generation high-resolution SNP arrays, Normal Karyotype (NK)-AML patients at diagnosis (Dx) and remission (R) phases, in order to determine the number of tumor-associated copy number abnormalities (CNAs) and copy neutral-loss of heterozygosity (CN-LOH) regions per patient and to identify possible recurring genomic abnormalities. The number of tumor-associated CNAs was detemined after comparison of 11 matched Dx/R samples using stringent conditions able to reduce the number of false positive CNAs. 8 additional unmatched Dx samples were included in the analysis of recurring CNAs and for detection of broad CN-LOH segments. With the exception of a single outlier case, a low number of CNAs per patient was detected (median value of 1 somatic loss or gain per patient). However, a high prevalence of CNAs (60-70% of the patients showed at least 1 tumor-associated gain or loss) and few recurring CNAs were observed, thus providing new hints towards identification of cooperating mutations. An extensive search of all CN-LOH regions > 1 Mb revealed only 3 broad regions (terminal 12Mb of 22q, terminal 27Mb of 1p and the whole chromosome 21) in three patients out of 19 (16%). CN-LOH of the whole chromosome 21 was responsible for homozygosity of a missense mutation (R80C) of RUNX1/AML1. Our study suggests that a relative submicroscopic copy number stability NK-AML genomes is associated with low recurrence of specific CNAs and CN-LOH in NK-AML patient population.
2010-12-31 | GSE21780 | GEO
Project description:We analysed, by last-generation high-resolution SNP arrays, Normal Karyotype (NK)-AML patients at diagnosis (Dx) and remission (R) phases, in order to determine the number of tumor-associated copy number abnormalities (CNAs) and copy neutral-loss of heterozygosity (CN-LOH) regions per patient and to identify possible recurring genomic abnormalities. The number of tumor-associated CNAs was detemined after comparison of 11 matched Dx/R samples using stringent conditions able to reduce the number of false positive CNAs. 8 additional unmatched Dx samples were included in the analysis of recurring CNAs and for detection of broad CN-LOH segments. With the exception of a single outlier case, a low number of CNAs per patient was detected (median value of 1 somatic loss or gain per patient). However, a high prevalence of CNAs (60-70% of the patients showed at least 1 tumor-associated gain or loss) and few recurring CNAs were observed, thus providing new hints towards identification of cooperating mutations. An extensive search of all CN-LOH regions > 1 Mb revealed only 3 broad regions (terminal 12Mb of 22q, terminal 27Mb of 1p and the whole chromosome 21) in three patients out of 19 (16%). CN-LOH of the whole chromosome 21 was responsible for homozygosity of a missense mutation (R80C) of RUNX1/AML1. Our study suggests that a relative submicroscopic copy number stability NK-AML genomes is associated with low recurrence of specific CNAs and CN-LOH in NK-AML patient population. Nineteen AML bone marrow samples were collected at the time of diagnosis (>90% blasts), defined as karyotypically-normal on the basis of standard metaphase cytogenetics (MC) and analysed by the Affymetrix SNP 6.0 arrays. In 11 of such cases (matched Dx) we obtained a bone marrow sample at the remission phase (matched R) of comparable high quality as evaluated by Contrast QC and MAPD values. In 8 cases (unmatched Dx) the corresponding R sample was not available or was not of comparable quality. As a reference set the publicly available data from 270 HapMap individuals were used.
2010-12-31 | E-GEOD-21780 | biostudies-arrayexpress
Project description:We analyzed, by last-generation high-resolution SNP arrays, colorectal adenocarcinoma samples and matched normal colonic tissues in order to determine the number of tumor-associated copy number abnormalities (CNAs) and copy neutral-loss of heterozygosity (CN-LOH) regions per patient and to identify possible recurring genomic abnormalities.
2018-08-31 | GSE80460 | GEO
Project description:Retinoblastoma (Rb) is a childhood cancer of the developing retina that begins in utero in response to bi-allelic inactivation of RB1 or MYCN amplification, accounting for up to 1% of all tumours in infancy. To gain insights into the transcriptional events of each state cell transition during Rb development, we developed two Rb models via retinal organoid differentiation of RB1 depleted human embryonic stem cell line (RB1-null hESCs) and RB1patient-specific induced pluripotent (iPSC) line harbouring RB1 biallelic mutation (c.2082delC). Both models were characterised by RB1 depletion and a significant increase in the fraction of proliferating cone precursors (RXRγ+Ki67+), which were defined as cell of origin for Rb by the single cell RNA-Seq analysis. The RB1 depleted retinal organoids displayed similar features to Rb tumours including mitochondrial cristae aberration and rosette-like structures and were able to undergo cell growth in an anchorage-independent manner, indicative of cell transformation in vitro. The patient-specific iPSC model displayed an enhanced reduction of amacrine, horizontal and retinal ganglion cells and an accelerated loss of cone photoreceptor markers during transition towards retinoma and Rb, compared to RB1-null hESC. In both models, the Rb cells of origin, intermediate retinoma and/or Rb cells expressed retinal ganglion and horizontal cell in addition to cone markers, a novel finding, which should help to better identify and eradicate these cells within the tumour mass. Application of Melphalan, Topotecan and TW-37 led to a significant reduction in the fraction of proliferating cone precursors, validating the suitability of these in vitro models for testing novel therapeutics for Rb.
2023-03-03 | GSE173447 | GEO
Project description:The action of RB as a tumor suppressor has been difficult to define, in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology with a genome wide analysis of gene expression and RB chromatin binding, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program. Binding of RB was examined in growing, quiescent, senescent or senescent cells lackign RB. Binding of p130 was examined in quiescent or senescent cells in the presence or absence of RB. Libraries were prapered from DNA co-precipiated with RB or p130 specific antibodies or from mock (beads-only) immunoprecipiates.
2010-01-15 | E-GEOD-19898 | biostudies-arrayexpress