Platinum Genomes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA347414 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:<p>Improvement of variant calling in next-generation sequence data requires a comprehensive, genome-wide catalogue of high-confidence variants called in a set of genomes for use as a benchmark. We generated deep, whole-genome sequence data of seventeen individuals in a three-generation pedigree and called variants in each genome using a range of currently available algorithms. We used haplotype transmission information to create a phased "platinum" variant catalogue of 4.7 million single nucleotide variants (SNVs) plus 0.7 million small (1-50bp) insertions and deletions (indels) that are consistent with the pattern of inheritance in the parents and eleven children of this pedigree. Platinum genotypes are highly concordant with the current catalogue of the National Institute of Standards and Technology for both SNVs (>99.99%) and indels (99.92%), and add a validated truth catalogue that has 26% more SNVs and 45% more indels. Analysis of 334,652 SNVs that were consistent between informatics pipelines yet inconsistent with haplotype transmission ("non-platinum") revealed that the majority of these variants are <i>de novo</i> and cell-line mutations or reside within previously unidentified duplications and deletions. The reference materials from this study are a resource for objective assessment of the accuracy of variant calls throughout genomes.</p>
| phs001224 | dbGaP
Project description:Resistance to platinum-based chemotherapy is a clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, innovative drugs against platinum-resistance are urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and cleaved into active cytostatic metabolites. Here, we explore the activity of the duplex-prodrug 5-FdU-ECyd, covalently linking 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), on platinum-resistant OC cells. RNA-Sequencing was used for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis.
2018-02-22 | GSE98230 | GEO
Project description:Yeast homozygous and essential heterozygous deletion mutants were screened against novel platinum-containing compounds
2012-08-28 | E-MTAB-1267 | biostudies-arrayexpress
Project description:Platinum compounds display clinical activity against a wide variety of solid tumors. However, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux-kinetics indicated that ATP11B enhances the export of cisplatin from cells. The co-localization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins such as syntaxin-6 (STX6) and vesicular associated membrane protein 4 (VAMP4) strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, silencing ATP11B expression might be a therapeutic strategy to overcome cisplatin resistance. We performed the transfection of control-siRNA and ATP11B-siRNA to both cisplatin-sensitive A2780-PAR and cisplatin-resistant A2780-CP20 cells respectively.
2013-01-23 | E-GEOD-43694 | biostudies-arrayexpress
Project description:This study aims at correlating changes in the transcriptional state in high grade serous epithelial ovarian cancer (HGS-EOC) to the response to therapy, in particular the insurgence of resistance to platinum-based treatment.
2020-02-11 | E-MTAB-7083 | biostudies-arrayexpress
Project description:This study aims at correlating changes in the microRNA state in high grade serous epithelial ovarian cancer (HGS-EOC) to the response to therapy, in particular the insurgence of resistance to platinum-based treatment.
2020-02-11 | E-MTAB-7084 | biostudies-arrayexpress
Project description:Resistance to platinum compounds represents a major obstacle to the cure of ovarian carcinoma. The molecular profiling of drug-sensitive and drug-resistant cells may be helpful to clarify if altered expression of miRNAs can contribute to the drug-resistant phenotype. The expression pattern of miRNAs of three ovarian carcinoma cell lines was examined. The analysis revealed the modulation of several miRNAs in the two platinum-resistant cell lines as compared to parental platinum-sensitive cells. The integration of the information obtained through miRNA expression analysis may be useful to clarify the specific molecular alterations of factors and pathway favouring survival of tumor cells.
2018-06-26 | GSE58469 | GEO
Project description:We demonstrate that 6mer seed toxicity plays a role in platinum resistance of ovarian cancer
2021-02-02 | GSE165145 | GEO
Project description:We demonstrate that 6mer seed toxicity plays a role in platinum resistance of ovarian cancer
2021-02-02 | GSE165147 | GEO