ArticleMolecular oncology2021
Promoter methylation of DNA homologous recombination genes is predictive of the responsiveness to PARP inhibitor treatment in testicular germ cell tumors.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Gemcitabine, carboplatin and veliparib in multiple relapsed/refractory germ cell tumours: The GCT-SK-004 phase II trial.Investigational new drugs · 2021Trial
- Driving precision medicine in testicular germ cell tumors: from preclinical models to clinical applications.Therapeutic advances in medical oncology · 2026Review
- Changes in methylation associated with development of metabolic syndrome in testicular cancer patients treated with cisplatin chemotherapy.Scientific reports · 2025Article
- PARP Inhibitors in Genitourinary Cancer: A New Paradigm Beyond Prostate Cancer.International journal of urology : official journal of the Japanese Urological Association · 2025Review
- MIR124-3 and NKX6-1 hypermethylation profiles accurately predict metachronous gastric lesions in a Caucasian population.Clinical epigenetics · 2024Article
- Expression of CD44 is associated with aggressiveness in seminomas.Molecular biology reports · 2024Article
- Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship.Biomedicines · 2024Review
- Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling.Signal transduction and targeted therapy · 2023Article
- The Interplay between Dysregulated Metabolism and Epigenetics in Cancer.Biomolecules · 2023Review
- Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients.International journal of molecular sciences · 2023Review
- DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation.Cancer medicine · 2023Article
- Effect of the PARP inhibitor veliparib on germ cell tumor cell lines.Oncology letters · 2022Article
- Article
- Review
- DNA Methylation Biomarkers for Prediction of Response to Platinum-Based Chemotherapy: Where Do We Stand?Cancers · 2022Review
- Reciprocal epigenetic remodeling controls testicular cancer hypersensitivity to hypomethylating agents and chemotherapy.Molecular oncology · 2022Article
- The component of the mJournal of experimental & clinical cancer research : CR · 2021Article
- Between a Rock and a Hard Place: An Epigenetic-Centric View of Testicular Germ Cell Tumors.Cancers · 2021Review
- Female Germ Cell Development, Functioning and Associated Adversities under Unfavorable Circumstances.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Testicular germ cell tumors (TGCTs) are the most common cancers in men aged 15-39 years and are divided into two major groups, seminomas and nonseminomas. Novel treatment options are required for these patients, to limit side effects of chemotherapy. We hypothesized that promoter methylation of relevant homologous recombination (HR) genes might be predictive of response to poly-ADP ribose polymerase inhibitors (PARPis) in TGCTs. We report a study pipeline combining in silico, in vitro, and clinical steps. By using several databases and in silico tools, we identified BRCA1, RAD51C, PALB2, RAD54B, and SYCP3 as the most relevant genes for further investigation and pinpointed specific CpG sites with pronounced negative correlation to gene expression. Nonseminomas displayed significantly higher methylation levels for all target genes, where increased methylation was observed in patients with more differentiated subtypes and higher disease burden. We independently performed second-line targeted validation in tissue series from TGCT patients. A moderate and/or strong anti-correlation between gene expression (assessed by RNA-sequencing) and promoter methylation (assessed by 450k array) was found, for all of the targets. As a proof of concept, we demonstrated the sensitivity of TGCT cell lines to Olaparib, which associated with differential methylation levels of a subset of targets, namely BRCA1 and RAD51C. Our findings support the use of HR genes promoter methylation as a predictor of the therapeutic response to PARPis in patients with TGCT.
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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.