ArticleBMC cancer2017
Lack of MRE11-RAD50-NBS1 (MRN) complex detection occurs frequently in low-grade epithelial ovarian cancer.
Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- The prevalence of mismatch repair deficiency in ovarian cancer: A systematic review and meta-analysis.International journal of cancer · 2022Pooled it
- Insights into Ovarian Cancer: Unraveling the Role of DNA Double-strand Break-related Genes in Pathogenesis and Therapeutic Avenues.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Review
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- PTEN inhibition enhances sensitivity of ovarian cancer cells to the poly (ADP-ribose) polymerase inhibitor by suppressing the MRE11-RAD50-NBN complex.British journal of cancer · 2024Article
- Molecular mechanism of PARP inhibitor resistance.Oncoscience · 2024Review
- Review
- Targeted next-generation sequencing of 21 candidate genes in hereditary ovarian cancer patients from the Republic of Bashkortostan.Journal of ovarian research · 2023Article
- Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma.Translational andrology and urology · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- DNA Repair Mechanisms, Protein Interactions and Therapeutic Targeting of the MRN Complex.Cancers · 2022Review
- Crosstalk between SUMOylation and ubiquitylation controls DNA end resection by maintaining MRE11 homeostasis on chromatin.Nature communications · 2022Article
- Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers.NPJ precision oncology · 2022Article
- Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy.Frontiers in oncology · 2022Article
- Rad50 promotes ovarian cancer progression through NF-κB activation.Journal of cellular and molecular medicine · 2021Article
- Development of the PARP inhibitor talazoparib for the treatment of advancedExpert opinion on pharmacotherapy · 2021Review
- Yeast-based screening of cancer mutations in the DNA damage response protein Mre11 demonstrates importance of conserved capping domain residues.Molecular biology reports · 2021Article
- Transient Response of Olaparib on Pulmonary Artery Sarcoma Harboring Multiple Homologous Recombinant Repair Gene Alterations.Journal of personalized medicine · 2021Article
- Clinicopathological and Functional Evaluation Reveal NBS1 as a Predictor of Platinum Resistance in Epithelial Ovarian Cancers.Biomedicines · 2021Article
- RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers.Molecular biomedicine · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBRCA1/2-deficient ovarian carcinomas are recognized as target for Poly (ADP-ribose) polymerase (PARP) inhibitors. BRCA1 and BRCA2 proteins are involved in homologous recombination repair of double-strand DNA breaks. The relevance of other homologous recombination repair proteins, e.g. MRE11, RAD50, NBS1 (MRN complex) in ovarian carcinomas is unclear. The objective of this study was to investigate the prevalence of lack of MRE11, RAD50, NBS1 protein detection in epithelial ovarian cancer (EOC).
methodsA tissue microarray (TMA) with 134 EOC was immunohistochemically evaluated for MRE11, RAD50 and NBS1. Data was analysed for associations with clinicopathological parameters, histological subtype, patient overall survival and mismatch repair (MMR) protein status. Sensitivity towards the PARP inhibitor BMN673 was tested in two ovarian cancer cell lines (TOV-21 and OVTOKO) using colony formation assays.
resultsLack of MRN complex protein detection was seen in 41% (55/134) of EOC and was more frequent in low-grade (57.6%; 19/33) than in high-grade EOC (18.8%; 36/101; n = 134; p = 0.04). There was an association with the ovarian carcinoma subtype (60.3%; 35/58 lack of detection in type I versus 26.3%; 20/76 in type II; n = 134; p < 0.001) as well as undetectable DNA mismatch repair proteins MLH1 and MSH2 (89.3%; 25/28; n = 131; p < 0.001). MRE11 knockdown led to moderately increased sensitivity towards the PARP inhibitor BMN673 in one ovarian carcinoma cell line in vitro.
conclusionsFrequent lack of MRE11, RAD50, NBS1 protein detection in type I human ovarian carcinomas is observed in EOC and our data suggests further investigation regarding sensitivity to PARP-inhibition in tumours lacking MRE11 expression.
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