ArticleClinical epigenetics2021
Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples.
Article in Clinical epigenetics, 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, 25 citations in OpenAlex.
- Identification and validation of liquid biopsy-based methylation biomarkers for germ cell tumor subtypes.Communications medicine · 2026Article
- Low-grade glial neoplasms of germ cell origin may represent maturation of embryonic-type neuroectodermal elements.Histopathology · 2026Article
- Treatment options in platinum-refractory male germ cell cancers: current standards and future directions.Therapeutic advances in medical oncology · 2026Review
- NanoString profiling of DNA repair and apoptosis genes in testicular germ cell tumours with divergent chemotherapy outcomes.Therapeutic advances in medical oncology · 2026Article
- Changes in methylation associated with development of metabolic syndrome in testicular cancer patients treated with cisplatin chemotherapy.Scientific reports · 2025Article
- MicroRNA-371-373 cluster and methylome analysis suggests that a subset of 'somatic-type' malignancies arising in germ cell tumors may originate in yolk sac tumor components.The Journal of pathology · 2025Article
- Exploring the molecular pathways of miRNAs in testicular cancer: from diagnosis to therapeutic innovations.Functional & integrative genomics · 2025Review
- Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship.Biomedicines · 2024Review
- The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors.Cancers · 2024Review
- Biomarkers for Salvage Therapy in Testicular Germ Cell Tumors.International journal of molecular sciences · 2023Review
- Children's Oncology Group's 2023 blueprint for research: Germ cell tumors.Pediatric blood & cancer · 2023Article
- Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients.International journal of molecular sciences · 2023Review
- CSNK1G2-AS1 promotes metastasis, colony formation and serves as a biomarker in testicular germ cell tumor cells.Journal of Cancer · 2023Article
- Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted.International journal of molecular sciences · 2022Review
- Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm.Life (Basel, Switzerland) · 2022Article
- Reciprocal epigenetic remodeling controls testicular cancer hypersensitivity to hypomethylating agents and chemotherapy.Molecular oncology · 2022Article
- Epigenetics and Testicular Cancer: Bridging the Gap Between Fundamental Biology and Patient Care.Frontiers in cell and developmental biology · 2022Review
- Morphological and molecular heterogeneity in testicular germ cell tumors: implications for dedicated investigations.Virchows Archiv : an international journal of pathology · 2021Article
- Identification of mRNA Prognostic Markers for TGCT by Integration of Co-Expression and CeRNA Network.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Testicular germ cell tumors (TGCTs) are among the most common solid malignancies in young-adult men, and currently most mortality is due to metastatic disease and emergence of resistance to cisplatin. There is some evidence that increased methylation is one mechanism behind this resistance, stemming from individual studies, but approaches based on matched primary and metastatic patient samples are lacking. Herein, we provide an EPIC array-based study of matched primary and metastatic TGCT samples. Histology was the major determinant of overall methylation pattern, but some clustering of samples related to response to cisplatin was observed. Further differential analysis of patients with the same histological subtype (embryonal carcinoma) disclosed a remarkable increase in net methylation levels (at both promoter and CpG site level) in the patient with cisplatin-resistant disease and poor outcome compared to the patient with complete response to chemotherapy. This further confirms the recent results of another study performed on isogenic clones of sensitive and resistant TGCT cell lines. Differentially methylated promoters among groups of samples were mostly not shared, disclosing heterogeneity in patient tissue samples. Finally, gene ontology analysis of cisplatin-resistant samples indicated enrichment of differentially hypermethylated promoters on pathways related to regulation of immune microenvironment, and enrichment of differentially hypomethylated promoters on pathways related to DNA/chromatin binding and regulation. This data supports not only the use of hypomethylating agents for targeting cisplatin-resistant disease, but also their use in combination with immunotherapies and chromatin remodelers.
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