ArticleGynecologic oncology2016
Copy number deletion of RAD50 as predictive marker of BRCAness and PARP inhibitor response in BRCA wild type ovarian cancer.
Article in Gynecologic oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- Development and validation of gene expression-based signature for high-grade serous ovarian cancer.Journal of ovarian research · 2026Article
- RAD50 missense variants differentially affect the DNA damage response and mitotic progression.FEBS letters · 2025Article
- Role of MRE11 in DNA damage repair pathway dynamics and its diagnostic and prognostic significance in hereditary breast and ovarian cancer.BMC cancer · 2025Article
- Landscape of homologous recombination deficiency in gastric cancer and clinical implications for first-line chemotherapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Targeting DNA damage repair mechanism by using RAD50-silencing siRNA nanoparticles to enhance radiotherapy in triple negative breast cancer.Materials today. Bio · 2024Article
- Targeting the Cdc2-like kinase 2 for overcoming platinum resistance in ovarian cancer.MedComm · 2024Article
- Limitations of homologous recombination status testing and poly (ADP-ribose) polymerase inhibitor treatment in the current management of ovarian cancer.Frontiers in oncology · 2024Review
- Prediction of Chemoresistance-How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer.Current oncology (Toronto, Ont.) · 2023Review
- Multi-scale characterisation of homologous recombination deficiency in breast cancer.Genome medicine · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- Article
- Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition?Cancers · 2022Review
- A Prognostic and Carboplatin Response Predictive Model in Ovarian Cancer: A Mono-Institutional Retrospective Study Based on Clinics and Pharmacogenomics.Biomedicines · 2022Article
- Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer, Part 1: Technical Considerations.Cancers · 2022Review
- Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy.Frontiers in oncology · 2022Article
- Relevance of Platinum-free Interval andClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Homologous Recombination Deficiency: Cancer Predispositions and Treatment Implications.The oncologist · 2021Review
- Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer.Cancers · 2021Review
- Genetic alterations and their therapeutic implications in epithelial ovarian cancer.BMC cancer · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveTo identify novel prognostic and therapeutic markers for PARP inhibitors in BRCA wild type ovarian cancer (OvCa).
methodsBRCAness status was defined by analyzing whole-exome deep sequencing data from 220 BRCAwt OvCa cases in TCGA. Thirty-three DNA-repair genes were screened in an integrated manner for BRCA-independent mechanism of BRCAness using multiple-dimensional genomic data. Publicly available databases and siRNA knock-down were used for external validation and evaluation of drug response in OvCa cell lines.
resultsIn 220 BRCAwt OvCa patients, tumors exhibiting the BRCAness signature have enhanced OS (HR [95% CI]=0.33 [0.15-0.69], P=0.004) and PFS (HR [95% CI]=0.51 [0.24-1.08], P=0.077), strongly suggesting a BRCA-independent mechanism of drug sensitivity in those patients. Systematic screening of driving molecular events of BRCAness revealed that RAD50 deletion is a marker of BRCAness. The RAD50 deletion occurred in 18% of BRCAwt OvCa patients. RAD50 deletion led to its decreased mRNA expression in tumors (fold change=0.63, P=3.56×10(-13)). In BRCAwt patients, RAD50 deletion was associated with significantly better OS (HR [95% CI]=0.44 [0.25-0.78], P=0.005) and PFS (HR [95% CI]=0.60 [0.37-0.99], P=0.044), adjusted by age and stage. Knockdown of RAD50 expression augmented OvCa cell's responses to cisplatin and olaparib. Among 19 OvCa cell lines, the RAD50 copy number deletion is significantly associated with better responses to two structurally distinct PARPis (i.e. olaparib and rucaparib).
conclusionOur study identified the copy number deletion of RAD50 as a candidate marker for survival and response to PARPis in BRCAwt OvCa tumors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.