ArticleOncotarget2016
CNS germinomas are characterized by global demethylation, chromosomal instability and mutational activation of the Kit-, Ras/Raf/Erk- and Akt-pathways.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- The Japan Society for Neuro-Oncology guideline on the diagnosis and treatment of central nervous system germ cell tumors.Neuro-oncology · 2022Guideline
- Cerebrospinal Fluid Genomic Profiling as an Adjunct in a Case of Intracranial Germinoma: Utility and Limitations.Diagnostics (Basel, Switzerland) · 2026Article
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- RRAS and RRAS2 Mutations Are Recurrent Oncogenic Drivers in Lung Cancer and Are Sensitive to the Pan-RAS Inhibitor RMC-6236.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Germline Predisposition in Pediatric Central Nervous System Tumors: Insights from a Multigene Panel Study.Oncology research · 2026Article
- Decisional Tree for Pineal Tumors.Advances and technical standards in neurosurgery · 2026Review
- Article
- Novel molecular subtypes of intracranial germ cell tumors expand therapeutic opportunities.Neuro-oncology · 2024Article
- Plasma miRNA expression profile in pediatric pineal pure germinomas.Frontiers in oncology · 2024Article
- Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors.Scientific reports · 2023Article
- Comparison of different predominant lesions in intracranial bifocal germ cell tumors to predict neuroendocrine outcomes.Endocrine connections · 2023Article
- Suprasellar pure germinoma mimicking low-grade glioma on neuroimaging.BMJ case reports · 2023Article
- Histogenesis of intracranial germ cell tumors: primordial germ cell vs. embryonic stem cell.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2023Review
- Signaling pathways in brain tumors and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Loss of liver kinase B1 in human seminoma.Frontiers in oncology · 2023Article
- Article
- Leveraging epigenomic patterns to resolve the heterogeneity and origins of CNS germ cell tumors.Neuro-oncology · 2022Article
- Article
- 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
- EANO, SNO and Euracan consensus review on the current management and future development of intracranial germ cell tumors in adolescents and young adults.Neuro-oncology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CNS germinomas represent a unique germ cell tumor entity characterized by undifferentiated tumor cells and a high response rate to current treatment protocols. Limited information is available on their underlying genomic, epigenetic and biological alterations. We performed a genome-wide analysis of genomic copy number alterations in 49 CNS germinomas by molecular inversion profiling. In addition, CpG dinucleotide methylation was studied by immunohistochemistry for methylated cytosine residues. Mutational analysis was performed by resequencing of candidate genes including KIT and RAS family members. Ras/Erk and Akt pathway activation was analyzed by immunostaining with antibodies against phospho-Erk, phosho-Akt, phospho-mTOR and phospho-S6. All germinomas coexpressed Oct4 and Kit but showed an extensive global DNA demethylation compared to other tumors and normal tissues. Molecular inversion profiling showed predominant genomic instability in all tumors with a high frequency of regional gains and losses including high level gene amplifications. Activating mutations of KIT exons 11, 13, and 17 as well as a case with genomic KIT amplification and activating mutations or amplifications of RAS gene family members including KRAS, NRAS and RRAS2 indicated mutational activation of crucial signaling pathways. Co-activation of Ras/Erk and Akt pathways was present in 83% of germinomas. These data suggest that CNS germinoma cells display a demethylated nuclear DNA similar to primordial germ cells in early development. This finding has a striking coincidence with extensive genomic instability. In addition, mutational activation of Kit-, Ras/Raf/Erk- and Akt- pathways indicate the biological importance of these pathways and their components as potential targets for therapy.
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