Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE26302 | GEO | 2011/09/09
SECONDARY ACCESSION(S): PRJNA135123
REPOSITORIES: GEO
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Project description:Chromosomal aberrations were studied both in a lung cancer cell line and colorectal cancer tumor samples. Results were verified by SKY karyotypes and by DNA ploidy analysis. The sensitivity of detecting chromosomal aberrations in tumor samples was evaluated by analyzing data from simulated mixtures of the lung cancer cell line H1395 and the normal cell line 1395BL from the same patient. Copy number analysis is presented on 12 colorectal cancer tumor samples and on in silico dilutions of a lung cancer cell line and its patient-matched blood cell line.
2011-09-08 | E-GEOD-26302 | biostudies-arrayexpress
Project description:Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways exist that limit the prevalence of such cells? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells. We find that chromosome mis-segregation leads to replication stress, generating further genomic instability, increased karyotype complexity, and ultimately cell cycle arrest. Cells with complex karyotypes exhibit features of senescence and a pro-inflammatory response that promotes their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that might well be a source of cancer cell immunosurveillance that must be overcome during malignant transformation.
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Project description:A cohort of 54 samples from the Barts Health NHS Trust (London) harbouring poor-risk cytogenetic aberrations including -7/del(7), -5/del(5), KMT2A rearrangements (other than t(9;11)), t(6;9), inv(3), -17/del(17) and complex karyotypes (≥ 3 chromosomal aberrations)
2023-05-11 | GSE213119 | GEO
Project description:Aneuploidy, while detrimental to untransformed cells, is notably prevalent in cancer. Aneuploidy is found as an early event during tumorigenesis which indicates that cancer cells have the ability to surmount the initial stress responses associated with aneuploidy, enabling rapid proliferation despite aberrant karyotypes. To generate more insight into key cellular processes and requirements underlying adaptation to aneuploidy, we generated a panel of aneuploid clones in p53-deficient RPE-1 cells and studied their behavior over time. As expected, de novo generated aneuploid clones initially displayed reduced fitness, enhanced levels of chromosomal instability and an upregulated inflammatory response. Intriguingly, after a prolonged period of culturing, aneuploid clones exhibited increased proliferation rates while maintaining aberrant karyotypes, indicative of an adaptive response to the aneuploid state. Interestingly, all adapted clones displayed reduced chromosomal instability (CIN) and reduced inflammatory signaling, suggesting that these are common aspects of adaptation to aneuploidy. Collectively, our data suggests that CIN and concomitant inflammation are key processes that require correction to allow for fast proliferation in vitro. Finally, we provide evidence that amplification of oncogenic KRAS can promote adaptation.
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Project description:In this study, we extend array CGH technology by making the accurate detection of chromosomal imbalances possible from a single fibroblast and blastomere following Phi29 DNA polymerase amplification. Firstly, array CGH experiments were performed on four different fibroblast cell lines, derived from patients affected by, respectively, trisomy 13, 18, 21, and monosomy X. For each cell line, three single cells were amplified. Following DNA amplification, all cells showed the expected DNA yields (n=12; 1.87 µg plus:minus 0.39). Sex-mismatch array CGH experiments were conducted on amplified DNA samples obtained from each cell. Sex chromosome ploidy levels, as well as all expected autosomal abnormalities were clearly identified. Secondly, we applied single-cell aneuploidy screening for the detection of chromosomal imbalances in preimplantation embryos. DNA from blastomeres from three 7-8 cell-stage embryos was amplified by ï¦29 DNA polymerase. Following DNA amplification, all cells yielded the expected amount of DNA (n=16; 2.45 µg plus:minus 0.41). Chromosomal aneuploidies were accurately detected using a simple and rapid array CGH protocol.
2010-07-01 | E-GEOD-3642 | biostudies-arrayexpress
Project description:Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration, and utilizes already available gene expression profiles to determine chromosomal aberrations.
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Project description:Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration, and utilizes already available gene expression profiles to determine chromosomal aberrations. RNA was extracted from different cell lines and analyzed for chromosomal stability using eSNP-Karyotyping
2016-07-04 | E-GEOD-81402 | biostudies-arrayexpress
Project description:Oral potentially malignant disorders (OPMDs) may precede oral squamous cell carcinoma (OSCC). Early detection of OPMDs has a crucial role in OSCC prevention. DNA aneuploidy and chromosomal aberrations are markers of genomic DNA damage and chromosomal instability (CIN), which is involved in cancer development. We explored the relationship among genomic DNA copy number aberrations (CNAs), histological diagnosis and DNA aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed for high resolution DNA flow cytometry (hr DNA-FCM) to determine the relative DNA content expressed with the DNA index (DI). Additionally, on a subset of these samples, array-Comparative Genomic Hybridization (aCGH) analysis was performed on DNA obtained from diploid nuclei suspension or from aneuploid-enriched nuclei suspensions. DNA copy number aberrations were determined using high resolution arrays on 151 samples (2x105K, n=82 samples, and 4x180K, n=69 samples) (Agilent Technologies, Palo Alto, CA, USA). Labeling, hybridization, scanning and feature extraction were performed as previously described using the cross hybridization method previously described [Castagnola P, Malacarne D, Scaruffi P, Maffei M, Donadini A, et al. (2011) Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue. BMC Cancer 11: 445.].
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Project description:Human mesenchymal stem cells (hMSC) are being successfully evaluated for the treatment of a wide range of pathological conditions, including graft versus host disease (GVHD), bone and cartilage degeneration, complex fistula and myocardial infarction. Many of these clinical trials use hMSC, which have been previously expanded in vitro for 8-12 weeks under pro-oxidative “standard” cell culture conditions. These conditions could have negative effects over genetic stability and promote mutations and chromosomal abnormalities. Our FISH (Fluorescence in situ hybridization) analysis shows that aneuploidy is not unusual phenomenon in conventional cultures of hMSC and that it progressively increases with the passages. We further demonstrate that senescence is linked to transcriptional deregulation of a set of genes that have been previously implicated in cancer and ploidy control. Overexpression of hTERT reversed the deregulation of these ploidy control genes and maintained the basal levels of ploidy even during long-term culture, through its canonical function of telomere elongation and by reducing the levels of oxidative stress. We propose that the high levels of aneuploidy and deregulation of these genes would be relevant biomarkers of senescence in standard cultures of hMSC.
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