ArticleProceedings of the National Academy of Sciences of the United States of America2010
DNA polymerase theta up-regulation is associated with poor survival in breast cancer, perturbs DNA replication, and promotes genetic instability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 1 of them a synthesis that pooled it.
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Who cites it
143 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
- Prognostic value of cyclin E expression in breast cancer: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Pooled it
- DNA polymerase theta (Polθ): a novel candidate for targeted cancer therapy.Cancer biology & therapy · 2026Review
- Pan-cancer multi-omics analysis reveals upregulation of the POLE2 subunit of DNA polymerase epsilon and its associations with patient survival and cellular pathways beyond DNA replication.NAR genomics and bioinformatics · 2026Article
- The Pharmacologic Profile of ART6043, a First-in-Class Clinical DNA Polymerase Theta Polymerase Domain Inhibitor Potentiating PARP Inhibitor Efficacy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- The polymerase milieu of human papillomavirus.Journal of virology · 2026Review
- Apoptosis-driven chromosomal rearrangements in cancer: CAD cleavage, nuclear architecture, and microhomology-mediated end joining.Oncogenesis · 2026Review
- Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- RTx-303, an Orally Bioavailable Polθ Polymerase Inhibitor That Potentiates PARP Inhibitors in BRCA Mutant Tumors.Journal of medicinal chemistry · 2025Article
- Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma.Journal of translational medicine · 2025Article
- Statistical and Evolutionary Analysis of Sequenced DNA from Breast Cancer FFPE Specimens.bioRxiv : the preprint server for biology · 2025Article
- POLQ mediated end-joining promotes DNA damage tolerance in neuroblastoma.Translational oncology · 2025Article
- Pan-Cancer Exome-wide analysis of germline mutational patterns and pathways.Scientific reports · 2025Article
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- A non-tethering role for the Drosophila Pol θ linker domain in promoting damage resolution.Nucleic acids research · 2025Article
- Review
- Structural basis for Polθ-helicase DNA binding and microhomology-mediated end-joining.Nature communications · 2025Article
- Review
- Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.NAR cancer · 2025Article
- Dynamic interplay of cNHEJ and MMEJ pathways of DNA double-strand break repair during embryonic development in zebrafish.Scientific reports · 2025Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 9 institutions in 5 countries.
Funding
Abstract
"Replicative stress" is one of the main factors underlying neoplasia from its early stages. Genes involved in DNA synthesis may therefore represent an underexplored source of potential prognostic markers for cancer. To this aim, we generated gene expression profiles from two independent cohorts (France, n=206; United Kingdom, n=117) of patients with previously untreated primary breast cancers. We report here that among the 13 human nuclear DNA polymerase genes, DNA Polymerase (POLQ) is the only one significantly up-regulated in breast cancer compared with normal breast tissues. Importantly, POLQ up-regulation significantly correlates with poor clinical outcome (4.3-fold increased risk of death in patients with high POLQ expression), and this correlation is independent of Cyclin E expression or the number of positive nodes, which are currently considered as markers for poor outcome. POLQ expression provides thus an additional indicator for the survival outcome of patients with high Cyclin E tumor expression or high number of positive lymph nodes. Furthermore, to decipher the molecular consequences of POLQ up-regulation in breast cancer, we generated human MRC5-SV cell lines that stably overexpress POLQ. Strong POLQ expression was directly associated with defective DNA replication fork progression and chromosomal damage. Therefore, POLQ overexpression may be a promising genetic instability and prognostic marker for breast cancer.
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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.