Similar Datasets
Project description:Paired platinum-sensitive & platinum-resistant cell lines PEO1 and PEO4 (respectively) were derived from the same patient. Cell line cultures were profiled with the HT-HGU133a GeneChip to investigate chemotherapy resistance related expression of genes marked with different histone modifications in a primary ovarian tumour (clinical data for the primary ovarian tumour is available as Series supplementary file). 4 replicates of each of the PEO1 and PEO4 cell line were profiled using the HT-HGU133a GeneChip
2012-10-12 | E-GEOD-41499 | biostudies-arrayexpress
Project description:Enhancers are regulatory elements of the genome involved in transcriptional regulation and reprogramming. Similarly, we propose that secondary DNA structures termed G-quadruplexes could also be impacting transcription in an enhancer based way via long-range interactions to bring together regulatory elements of the genome. In this study, we map G-quadruplex structures and h3k27ac enhancer marks in a paired ovarian cancer cell line; PEO1 and PEO4. We endeavour to use these findings to help link the transcriptional function of G-quadruplexes with enchancer in chemotherapy sensitive (PEO1) and chemotherapy resistant (PEO4) ovarian cancer cells.
2025-06-06 | GSE279641 | GEO
Project description:Sequencing of olaparib-resistant PEO1 derivatives (C4, C5, C10 and C18) and parental PEO1 (P1 and P2) cells was performed in order to determine mechanisms of acquired resistance in the resistant cell lines. PEO1 parental cell lines were authenticated prior to sequencing. PEO1 parental were confirmed to be BRCA2-mutated (5139C>G). Olaparib PEO1 resistant cells were generated through a step-wise escalation of olaparib (10nM to 8uM olaparib). In olaparib resistant lines an increase canonical Wnt signaling and loss of of non-canonical Wnt signaling was observed.
2018-07-28 | GSE117765 | GEO
Project description:Deleterious alterations of the gene encoding BRCA2, a protein involved in homologous recombination (HR), contribute to the pathogenesis of a subset of ovarian, breast, prostate and pancreatic cancers as well as their increased sensitivity to platinating agents and poly(ADP-ribose) polymerase inhibitors (PARPis). While secondary mutations that restore a functional BRCA2 protein are detected in a fraction of cases that become drug resistant, the causes of resistance in other cases are poorly understood. Here we characterized clones derived from the BRCA2-mutant ovarian cancer line PEO1 by PARPi selection. Colony forming assays demonstrated cross-resistance of these clones to multiple PARPis, cisplatin and doxorubicin. Despite persistence of the signature 4965C>G (p.Y1655X) BRCA2 nonsense mutation, HR was restored in the resistant cells. Immunoprecipitation followed by immunoblotting or mass spectrometry demonstrated expression of low levels of BRCA2 protein, including peptides distal to the premature termination codon. Reporter assays demonstrated readthrough selective for the UAG stop codon in the resistant clones but not parental PEO1 cells. Mass spectrometry and immunoblotting provided evidence for readthrough of stop codons, particularly UAGs, in additional proteins in the resistant clones. BRCA2 gene interruption either 5’ or 3’ to the stop codon restored sensitivity of the resistant clones to PARPis and cisplatin, implicating the low level BRCA2 expression in resistance. Accordingly, the present results identify low level readthrough of nonsense codons as a potential mechanism of drug resistance that might need to be considered when assessing the impact of BRCA2 nonsense mutations.
2024-09-01 | GSE243142 | GEO
Project description:G-quadruplexes are secondary DNA structures which have been shown to have an impact on gene transcription via a variety of mechanisms, In this study we generate RNA-seq data of wildtype chemotherpay sensitive (PEO1 A) and chemostherapy resistant (PEO4 A) ovarian cancer cells to intersect with G-quadruplex mapping data to assess how transcription is impacted by G-quadruplex formation. In another variation of the PEO1/4 cell line, in which the PEO1 B cell line has a reversion mutation to reinstate BRCA2, we used the G-quadruplex stabilising molecule pyridostatin (PDS) to treat PEO1 B and its counterpart PEO4 B for either 0, 2 or 6 hours to see how stabilising G-quadruplexes effects gene expression in a temporal manner.
2025-06-06 | GSE279501 | GEO
Project description:Deleterious alterations of the gene encoding BRCA2, a protein involved in homologous recombination (HR), contribute to the pathogenesis of a subset of ovarian, breast, prostate and pancreatic cancers as well as their increased sensitivity to platinating agents and poly(ADP-ribose) polymerase inhibitors (PARPis). While secondary mutations that restore a functional BRCA2 protein are detected in a fraction of cases that become drug resistant, the causes of resistance in other cases are poorly understood. Here we characterized clones derived from the BRCA2-mutant ovarian cancer line PEO1 by PARPi selection. Colony forming assays demonstrated cross-resistance of these clones to multiple PARPis, cisplatin and doxorubicin. Despite persistence of the signature 4965C>G (p.Y1655X) BRCA2 nonsense mutation, HR was restored in the resistant cells. Immunoprecipitation followed by immunoblotting or mass spectrometry demonstrated expression of low levels of BRCA2 protein, including peptides distal to the premature termination codon. Reporter assays demonstrated readthrough selective for the UAG stop codon in the resistant clones but not parental PEO1 cells. Mass spectrometry and immunoblotting provided evidence for readthrough of stop codons, particularly UAGs, in additional proteins in the resistant clones. BRCA2 gene interruption either 5’ or 3’ to the stop codon restored sensitivity of the resistant clones to PARPis and cisplatin, implicating the low level BRCA2 expression in resistance. Accordingly, the present results identify low level readthrough of nonsense codons as a potential mechanism of drug resistance that might need to be considered when assessing the impact of BRCA2 nonsense mutations.
2025-10-22 | GSE243141 | GEO
Project description:Paired platinum-sensitive & platinum-resistant cell lines PEO1 and PEO4 (respectively) were derived from the same patient. Cell line cultures were profiled with the HT-HGU133a GeneChip to investigate chemotherapy resistance related expression of genes marked with different histone modifications in a primary ovarian tumour (clinical data for the primary ovarian tumour is available as Series supplementary file).
2012-10-12 | GSE41499 | GEO
Project description:G-quadruplex ChIP-seq has been performed to establish genomic maps of G-quadruplex structures in chemotherapy sensitive (PEO1) and chemotherapy resistant (PEO4) ovarian cancer cell lines to uncover how the changes in G-quadruplex landscape may contribute to the development of chemotherapy resistance for the first time.
2025-06-06 | GSE279497 | GEO
Project description:Chromatin accessibilty is a key regulator of gene expression. In this study we aim to map accessible chromatin regions in both chemotherapy sensitive (PEO1) and chemotherapy resistant (PEO4) ovarian cancer cell lines, to intersect with RNA-seq data to see how chromatin architecture changes and impacts gene expression between the two cell lines.
2025-06-06 | GSE279495 | GEO
Project description:Alteration of the gene encoding BRCA2, a protein involved in homologous recombination (HR), by missense or nonsense mutations results in sensitivity of a subset of breast and ovarian cancers to platinating agents and poly(ADP-ribose) polymerase (PARP) inhibitors. Conversely, resistance to these agents is often accompanied by secondary BRCA2 mutations that restore a functional protein. Here we characterized clones derived from the BRCA2-mutant ovarian cancer line PEO1 by selection with the PARP inhibitor veliparib. Colony forming assays demonstrated cross-resistance of the resulting clones to multiple PARP inhibitors and cisplatin. Despite the continued presence of a 4965C>A (p.Y1655X) BRCA2 nonsense mutation, HR was restored in the resistant cells. Immunoprecipitation followed by immunoblotting or mass spectrometry demonstrated expression of low levels of BRCA2 protein, including peptides distal to the premature termination codon. Reporter assays demonstrated readthrough selective for the UAG stop codon in the veliparib-resistant clones but not parental PEO1 cells; and mass spectrometry revealed insertion of tyrosine rather than termination in the readthrough product. Mass spectrometry and immunoblotting provided evidence for readthrough of UAGs in additional proteins in the resistant clones. BRCA2 gene interruption 3’ to the stop codon restored sensitivity of the resistant clones to PARP inhibitors and cisplatin, implicating the low level BRCA2 expression in resistance. Accordingly, the present results identify low level readthrough of nonsense codons as a potential mechanism of drug resistance that might need to be considered when assessing the impact of mutations on the biology of cancers.
2025-10-27 | PXD037989 | Pride