ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2008
Global DNA hypomethylation in intratubular germ cell neoplasia and seminoma, but not in nonseminomatous male germ cell tumors.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Pooled it
- Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review.Targeted oncology · 2018Pooled it
- Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors.Molecular oncology · 2016Trial
- Bridging Andrology and Oncology: Prognostic Indicators of Cancer Among Infertile Men.Current issues in molecular biology · 2025Review
- Defining ortholog-specific UHRF1 inhibition by STELLA for cancer therapy.Nature communications · 2025Article
- RAS/Mitogen-Activated Protein Kinase Signaling Pathway in Testicular Germ Cell Tumors.Life (Basel, Switzerland) · 2024Review
- Article
- Clonal diversification and histogenesis of malignant germ cell tumours.Nature communications · 2022Article
- Testicular cancer in mice: interplay between stem cells and endocrine insults.Stem cell research & therapy · 2022Article
- 12p gain is predominantly observed in non-germinomatous germ cell tumors and identifies an unfavorable subgroup of central nervous system germ cell tumors.Neuro-oncology · 2022Article
- Overcoming Chemotherapy Resistance in Germ Cell Tumors.Biomedicines · 2022Review
- Gene expression microarray analysis of adult testicular germ cell tumor: a comparison between pure-type seminomas and seminoma components in mixed tumors.Virchows Archiv : an international journal of pathology · 2021Article
- The regulation mechanisms and the Lamarckian inheritance property of DNA methylation in animals.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Review
- Molecular and epigenetic pathogenesis of germ cell tumors.Asian journal of urology · 2021Review
- In Search of TGCT Biomarkers: A ComprehensiveDisease markers · 2020Article
- Article
- Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology.International journal of molecular sciences · 2019Review
- Cell-to-cell variation of chromosomal number in the adult testicular germ cell tumors: a comparison of chromosomal instability among histological components and its putative role in tumor progression.Virchows Archiv : an international journal of pathology · 2019Article
- Human Germ Cell Tumors are Developmental Cancers: Impact of Epigenetics on Pathobiology and Clinic.International journal of molecular sciences · 2019Review
- On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular Cancer.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Alterations in methylation of CpG dinucleotides at the 5 position of deoxycytidine residues (5(m)C) are a hallmark of cancer cells, including testicular germ cell tumors. Virtually all testicular germ cell tumors are believed to be derived from intratubular germ cell neoplasia unclassified (IGCNU), which is thought to arise from primordial germ cells. Prior studies revealed that seminomas contain reduced levels of global DNA methylation as compared with nonseminomatous germ cell tumors. Smiraglia et al have proposed a model whereby seminomas arise from IGCNU cells derived from primordial germ cells that have undergone 5(m)C erasure, and nonseminomas arise from IGCNU cells derived from primordial germ cells that have already undergone de novo methylation after the original erasure of methylation and contain normal 5(m)C levels. Yet the methylation status of IGCNU has not been determined previously. We used immunohistochemical staining against 5(m)C to evaluate global methylation in IGCNU and associated invasive testicular germ cell tumors. Strikingly, staining for 5(m)C was undetectable (or markedly reduced) in the majority of IGCNU and seminomas, yet there was robust staining in nonseminomatous germ cell tumors. The lack of staining for 5(m)C in IGCNU and seminomas was also found in mixed germ cell tumors containing both seminomatous and nonseminomatous components. Lack of 5(m)C staining was not related to a lack of the maintenance methyltransferase (DNA methyltransferase 1) protein. We conclude that testicular germ cell tumors are derived in most cases from IGCNU cells that have undergone developmentally programmed 5(m)C erasure and that the degree of subsequent de novo methylation is most closely related to the differentiation state of the neoplastic cells. That is, IGCNU cells and seminoma cells remain unmethylated, whereas all other histological types appear to arise after de novo methylation.
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