Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2
Abstract
1. Introduction
2. The Epigenetic Landscape of NF1
2.1. An Overview of NF1
2.2. The Role of Epigenetic Mechanisms in NF1 Pathogenesis
2.2.1. DNA Methylation
2.2.2. Non-Coding RNAs
2.3. The Prognostic Impact of Epigenetic Alterations in NF1
2.3.1. DNA Methylation
2.3.2. Histone Modifications
2.3.3. Non-Coding RNAs
3. The Epigenetic Architecture of NF2
3.1. An Overview of NF2
3.2. Epigenetic Drivers of NF2 Pathogenesis
3.2.1. DNA Methylation
3.2.2. Non-Coding RNAs
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ANRIL | Antisense non-coding RNA in the INK4 locus |
CDKN2A | Cyclin-dependent kinase inhibitor 2A |
CNF | Cutaneous neurofibroma |
CpG | Cytosine–phosphate–guanine |
CRE | cAMP response element |
DNA | Deoxyribonucleic acid |
EED | Embryonic ectoderm development |
ERK | Extracellular signal-regulated kinase |
H3K27me3 | Trimethylation of lysine 27 on histone H3 |
HGAP | High-grade astrocytomas with piloid features |
HOX | Homeobox |
KDM4 | Lysine demethylase 4 |
KDM6 | Lysine demethylase 6 |
LncRNA | Long non-coding RNA |
MAP2K3 | Mitogen-activated protein kinase 3 |
MEK | Mitogen-activated protein kinase |
MET | MET proto-oncogene, receptor tyrosine kinase |
miRNA | MicroRNA |
MKK3 | Mitogen-activated protein kinase 3 |
MLH1 | MutL homolog 1 |
MMP2 | Matrix metalloproteinase 2 |
MPNST | Malignant peripheral nerve sheath tumour |
mRNA | Messenger ribonucleic acid |
MSH2 | MutS homolog 2 |
MSH6 | MutS homolog 6 |
MSP | Methylation-specific PCR |
ncRNA | Non-coding RNA |
NF-CAR | Neurofibromatosis consensus area of regulation |
NF1 | Neurofibromatosis type 1 |
NF1HCS | NF1 5′ highly conserved sequence |
NF2 | Neurofibromatosis type 2 |
NF2-SWN | NF2-related schwannomatosis |
p53 | Tumour suppressor p53 |
PCR | Polymerase chain reaction |
PMEPA1 | Prostate transmembrane protein, androgen induced 1 |
PMS2 | Postmeiotic segregation increased 2 |
PNF | Plexiform neurofibroma |
PRC2 | Polycomb repressive complex 2 |
RAS | Rat sarcoma virus oncogene |
RASSF1A | Ras association domain family member 1 isoform A |
RNA | Ribonucleic acid |
rs2151280 | Reference SNP ID 2151280 |
SAM | S-adenosylmethionine |
SK-ES-1 | Human Ewing sarcoma cell line |
SNP | Single-nucleotide polymorphism |
SP1 | Specificity protein 1 |
SUZ12 | Suppressor of zeste 12 |
TALGN | Transgelin |
TF | Transcription factor |
U-251 MG cells | Uppsala 251 Malignant Glioma cells |
UTR | Untranslated region |
VS | Vestibular schwannoma |
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Epigenetic Mechanism | Key Mediator | Impact | Effect of Modification | Ref. |
---|---|---|---|---|
DNA Methylation | NF2 promoter methylation | Yes | Leads to NF2 gene silencing, which may contribute to tumourigenesis | [76] |
DNA Methylation | Methylation of three CpG sites within NF-CAR, a cis-acting regulatory region in the promoter of the NF2 gene | Yes | Inactivation of NF2, which leads to the development of schwannomas and other tumours in NF2 patients | [77] |
DNA Methylation | Hypomethylation at HOX genes in several CpG sites; MiRNA-21, MET, and PMEPA1 showed promoter hypomethylation | Yes | Enhances oncogenic miRNA and gene expression; leads to pathogenesis of the vestibular schwannomas | [78] |
DNA Methylation | No aberrant hypermethylation of the NF2 gene promoter region was found | No | Alternative mechanisms play a more critical role in the pathogenesis of vestibular schwannomas | [68] |
MicroRNAs | MiR-10b, miR-206, miR-183, and miR-204 showed downregulation; miR-431, miR-221, miR-21, and miR-720 showed upregulation; non-coding RNAs in the 14q32 chromosomal region showed upregulation | Yes | Contributes to the development of schwannomas | [79] |
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Stylianides, C.; Hadjigavriel, G.; Theotokis, P.; Vakirlis, E.; Meditskou, S.; Manthou, M.E.; Dermitzakis, I. Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2. Epigenomes 2025, 9, 30. https://doi.org/10.3390/epigenomes9030030
Stylianides C, Hadjigavriel G, Theotokis P, Vakirlis E, Meditskou S, Manthou ME, Dermitzakis I. Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2. Epigenomes. 2025; 9(3):30. https://doi.org/10.3390/epigenomes9030030
Chicago/Turabian StyleStylianides, Christina, Gavriel Hadjigavriel, Paschalis Theotokis, Efstratios Vakirlis, Soultana Meditskou, Maria Eleni Manthou, and Iasonas Dermitzakis. 2025. "Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2" Epigenomes 9, no. 3: 30. https://doi.org/10.3390/epigenomes9030030
APA StyleStylianides, C., Hadjigavriel, G., Theotokis, P., Vakirlis, E., Meditskou, S., Manthou, M. E., & Dermitzakis, I. (2025). Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2. Epigenomes, 9(3), 30. https://doi.org/10.3390/epigenomes9030030