Copy Number Variation in Brca2 (G25R) variant mouse tumors
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE84854 | GEO | 2016/07/27
SECONDARY ACCESSION(S): PRJNA335371
REPOSITORIES: GEO
Similar Datasets
Project description:To understand the overall amount of genomic instability seen in various genotypes of Brca2 (G25R) and to see where common gains and losses occur within a Trp53 heterozygous genetic background Comparing mouse tumor DNA with mouse genomic DNA
2016-07-27 | E-GEOD-84854 | biostudies-arrayexpress
Project description:Hypothesis: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. Results: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n=50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term survivors. In squamous cell carcinoma (n=28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, mRNA expression levels of corresponding genes were increased or decreased, respectively. Conclusion: Comprehensive tumor profiling permits the integration of genomic, histologic and clinical data. We identified gene copy number gains and losses, with corresponding changes in mRNA levels, that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.
2011-11-01 | GSE28572 | GEO
Project description:Neuroblastoma is a tumour of the sympathetic nervous system, with a clinical phenotype resulting from complex patterns of genetic abnormalities, accounting for the most common extracranial neoplasia in childhood. Here we report 44 copy number variations, validated by qPCR, in paired tumour and blood samples of seven patients with neuroblastoma. Thirty four genes were included in altered regions while 11 altered regions did not apparently contain known genes. Five changes were present both in tumour and blood DNA samples in four patients, suggesting presence of germline and/or somatic changes maintained throughout tumorigenesis. Furthermore, some similar or identical changes were observed in different patients. The X chromosome showed the largest number of alterations. DNA from peripheral blood and tumour samples was isolated following using Qiagen DNA Blood Mini Kit. Microarray assays were performed in an Affymetrix platform with Cytogenetics Whole-Genome 2.7 M Array® (Affymetrix, Inc., Santa Clara, CA) for detecting copy number variation across coverage of the whole genome with the highest density of markers for superior resolution. Assays were performed following the procedure of Cytogenetics Copy Number Assay User Guide (Affymetrix®) and analysed with the Affymetrix® Chromosome Analysis Suite (ChAS) software. Gains and losses in tumour and blood samples from each patient were estimated with 95% confidence intervals.
2014-01-01 | E-GEOD-43454 | biostudies-arrayexpress
Project description:Abnormalities provoked in human cells heterozygous for clinically relevant truncating mutations in BRCA2 by their exposure to naturally occurring aldehydes define a mechanism promoting carcinogenesis in mutation carriers. The ubiquitous metabolite and environmental toxin, formaldehyde, triggers replication fork instability and structural chromosomal aberrations in BRCA2 heterozygous cells. These abnormalities arise from a previously unrecognized effect of formaldehyde to selectively induce the proteasomal degradation of BRCA2, inducing functional haploinsufficiency only in cells where BRCA2 expression is already compromised by a heterozygous mutation. Similar effects are observed with acetaldehyde, a toxic product of alcohol catabolism. Replication fork instability and chromosomal aberrations in aldehyde-exposed cells arise from the unscheduled accumulation of RNA-DNA hybrids, revealing a mechanism driving genomic instability in BRCA2 heterozygous cells. We propose a model for cancer pathogenesis in which aldehyde exposure unmasks the carcinogenic potential of heterozygous BRCA2 mutations, with public health implications in mutation carriers.
2017-06-02 | PXD006106 | Pride
Project description:Brca2(fl/fl)Trp53(fl/fl) mice were crossed with MMTV-cre mice to create mice with both alleles of Brca2 and one allele of Trp53 deleted (refered to as Brca2KO). Mature luminal, luminal progenitor and basal mammary epithelial cell populations were sorted from Brca2KO and wildtype mice. Transcriptional profiling revealed marked perturbation within the luminal Brca2KO compartment
2023-12-06 | GSE232631 | GEO
Project description:Hypothesis: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. Results: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n=50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term survivors. In squamous cell carcinoma (n=28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, mRNA expression levels of corresponding genes were increased or decreased, respectively. Conclusion: Comprehensive tumor profiling permits the integration of genomic, histologic and clinical data. We identified gene copy number gains and losses, with corresponding changes in mRNA levels, that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung. Short-term (<20 months; n=53) and long-term survivors (>58 months;n=47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh-frozen tumor specimens. The samples were analyzed using high-resolution SNP-array technology. The molecular data was combined with information on clinical parameters.
2011-11-01 | E-GEOD-28572 | biostudies-arrayexpress
Project description:Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) present in 48 clear cell renal cell carcinoma (ccRCC) genomes result in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes are mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs are classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turn out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. Finally, the diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) are successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreases with the number of G3 related gene losses plus the total number of gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.
2017-06-09 | GSE95239 | GEO
Project description:Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and their matched normal samples. We detected a total of 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20% of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5%) and 17p13.1 (2.5%) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of TP53 or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains, which includes ETS1 and FLI1 genes. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development.
2016-01-22 | GSE71386 | GEO
Project description:The discovery of copy number variation in healthy individuals is far from complete, and due to the resolution of detection systems used, the majority of loci reported so far are relatively large (~65% > 10kb). Applying a two-stage high-resolution array CGH approach to analyse 50 healthy Caucasian males from northern France, we discovered 2208 copy number variants (CNVs) detected by more than one consecutive probe. These clustered into 1469 copy number variant regions (CNVRs), of which 721 are thought to be novel. The majority of these are small (median size 4.4kb) and most have common boundaries, with a coefficient of variation less than 0.1 for 83% of end-points in those observed in multiple samples. Only 6% of the CNVRs analysed showed evidence of both copy number losses and gains at the same site. A further 6089 variants were detected by single probes: 48% of these were observed in more than one individual. In total, 2570 genes were seen to intersect variants: 1284 in novel loci. Genes involved in differentiation and development were significantly overrepresented, and approximately half the genes identified feature in the OMIM database. The biological importance of many of the genes affected, along with the well-conserved nature of the majority of the copy number variants, suggests they could have important implications for phenotype and, thus, be useful for association studies of complex diseases. Keywords: comparative genomic hybridization
2007-08-14 | GSE8691 | GEO
Project description:In order to screen potential novel 'driver genes' in lung cancer in Xuanwei (LCXW), genome-wide DNA copy number alterations (CNAs) were detected on 8 paired LCXW and non-cancerous lung (NCL) tissues by array-based comparative genomic hybridization microarrays. The log2 copy-number ratio calculation and CNA calls were determined using segMNT algorithm in NimbleScan. Log2 ratio test/control thresholds of 0.25 and -0.25 were defined as copy number gains and losses, respectively. Deviant signal intensity ratios involving 5 or more neighboring probes were considered as genomic aberrations. A large number of CNAs and DEGs were detected, respectively. Many recurrent CNAs were screened out, including gains at 5p15.33-p15.32, 5p15.1-p14.3 and 5p14.3-p14.2, and losses at 11q24.3, 21q21.1, 21q22.12-q22.13 and 21q22.2.
2016-10-22 | GSE89046 | GEO