Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Copy Number Variation in Brca2 (G25R) variant mouse tumors

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Shyam Sharan

PROVIDER: E-GEOD-84854 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Copy Number Variation in Brca2 (G25R) variant mouse tumors

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

2016-07-27 | GSE84854 | GEO

RNA-seq profiling of mammary epithelial cell populations from Brca2 knockout and wildtype mice

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

SILAC proteomics analysis to assess differences in protein expression upon BRCA2 inactivation

Project description:BRCA2 maintains genome stability by facilitating DNA repair via homologous recombination and replication fork stability. Loss of BRCA2 is deleterious for survival of normal cells, but is paradoxically tolerated in cancer cells. Using quantitative mass-spectrometry, differences in protein expression were identified that might shed light on how breast cancer cells (HCC38) survive in the absence of BRCA2.

2018-12-19 | PXD007253 | Pride

Aldehyde exposure unmasks genome instability in cells heterozygous for clinically relevant BRCA2 mutations

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

Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories

Project description:Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.

2017-01-10 | GSE80685 | GEO

Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers

Project description:This SuperSeries is composed of the following subset Series: GSE32124: Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers [expression data] GSE32258: Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers [SNP data] Refer to individual Series

2012-02-01 | E-GEOD-32259 | biostudies-arrayexpress

Deletion of chromosome 13q and 14q is a common feature of tumors with BRCA2 mutations

Project description:Genomic profiling to identify common features of breast tumors with BRCA2 mutations. Gene expression data and genomic profiling data were used to identify common features of breast tumors with BRCA2 mutations. The associated expression data and genomic data are either present in Array-express under accession number E-TABM-854 or undergoing submission.

2012-11-23 | E-GEOD-39710 | biostudies-arrayexpress

Disseminated medulloblastoma in a child with germline BRCA2 6174delT mutation and without Fanconi anemia

Project description:We describe an 8 year old child who had disseminated anaplastic medulloblastoma and a deleterious heterozygous BRCA2 6174delT germline mutation. Molecular profiling was consistent with Group 4 medulloblastoma. The posterior fossa mass was resected and the patient received intensive chemotherapy and craniospinal irradiation. Despite this, the patient succumbed to a second recurrence of his medulloblastoma, which presented eight months after diagnosis as malignant pleural and peritoneal effusions. Continuous medulloblastoma cell lines were isolated from the original tumor (CHLA-01-MED) and the malignant pleural effusion (CHLA-01R-MED). Here we provide their analyses, including in vitro and in vivo growth, drug sensitivity, comparative genomic hybridization and next generation sequencing analysis. In addition to the BRCA2 6174delT, the medulloblastoma cells had amplification of MYC, deletion at Xp11.2 and isochromosome 17, but no structural variations or overexpression of GFI1 or GFI1B. To our knowledge, this is the first pair of diagnosis/recurrence medulloblastoma cell lines, the only medulloblastoma cell lines with BRCA2 6174delT described to date, and the first reported case of a child with medulloblastoma associated with a germline BRCA2 6174delT who did not also have Fanconi anemia. Continuous medulloblastoma cell lines were isolated from the original tumor (CHLA-01-MED) and the malignant pleural effusion (CHLA-01R-MED). Here we provide their analyses, including in vitro and in vivo growth, drug sensitivity, comparative genomic hybridization with Agilent 400k CGH arrays and whole transcriptome RNASeq analysis.

2015-07-06 | E-GEOD-70003 | biostudies-arrayexpress

MiDAS in BRCA2-deficient cells originate at early S-phase transcription-replication conflicts

Project description:Multiple replication abnormalities cause cells lacking BRCA2 to enter mitosis with under-replicated DNA and to activate mitotic DNA synthesis (MiDAS). However, the precise position of these MiDAS sites, as well as their origin, remains unknown. Here we labelled mitotic nascent DNA and performed high-throughput sequencing to identify at high-resolution the sites where MiDAS occurs in the absence of BRCA2. This approach revealed 150 genomic loci affected by MiDAS, which map within regions replicating during early S-phase and are therefore distinct from the aphidicolin-induced common fragile sites. Moreover, these sites largely localise near early firing origins and within genes transcribed in early S, suggesting that they stem from transcription-replication conflicts (TCRs). Inhibiting transcription with 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) during early S-phase abrogates MiDAS. Strikingly, MiDAS sites co-localise with genomic loci where R-loops form in unchallenged conditions, suggesting that R-loop accumulation caused by BRCA2 inactivation leads to DNA lesion which are repaired by MiDAS. RAD52 is required in this process, as its abrogation in BRCA2-deficient cells reduces the rate of MiDAS and causes DNA damage accumulation in G1. Furthermore, MiDAS sites triggered by BRCA2 inactivation are hotspots for genomic rearrangement in BRCA2-mutated breast tumours. These results indicate that BRCA2 acts in early S-phase to protect TRC- and R-loop-induced DNA lesions, thereby preventing them from becoming a source of genomic instability and tumorigenesis.

2022-08-01 | GSE196163 | GEO

brca2 and trp53 deficient mouse tumours

Project description:Whole-exome DNA sequence analysis of Brca2 and Trp53 deficient mouse mammary gland tumours

| PRJEB6674 | ENA