Abstract
Epigenetic mechanisms are crucial for normal development and maintenance of tissue-specific gene expression patterns in mammals. Impaired epigenetic processes can cause alterations in gene function and malignant cellular transformation. It is now known that epigenetic abnormalities, together with genetic changes, have a role in the onset and progression of cancer, which was once thought to be a genetic disease. Recent developments in the field of cancer epigenetics have demonstrated substantial reprogramming of all elements of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, and non-coding RNAs. DNA methyltransferases, histone acetyltransferases, and histone deacetylases are a few examples of epigenetic regulatory enzymes that are involved in epigenetic modification. In recent years, an increasing number of studies have demonstrated that mutations in epigenetic regulatory enzymes occur in various cancer types and are closely associated with the malignant phenotype. Hence, research on inhibitors that target these mutant enzymes has gradually shifted into preclinical and clinical stages. In this chapter, we first discuss the epigenetic regulatory enzymes and then how their mutations are associated with carcinogenesis.
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Abbreviations
- 5′-C:
-
5′-Residue of cytosine
- 5caC:
-
5-Carboxylcytosine
- 5fC:
-
5-Formylcytosine
- 5hmC:
-
5-Hydroxymethylcytosine
- 5hmU:
-
5-Hydroxymethyluracil
- α-KG:
-
α-Ketoglutarate
- ADD:
-
ATRX-DNMT3-DNMT3L domain
- ALL:
-
Acute lymphoblastic leukemia
- AML:
-
Acute myeloid leukemia
- ATC:
-
Anaplastic thyroid carcinoma
- ATM:
-
Ataxia telangiectasia mutant
- BAH1 and BAH2:
-
Bromo-adjacent homology 1 and 2
- BER:
-
Base excision repair
- BRCA1:
-
Breast cancer gene-1
- BRD:
-
Bromodomain
- CARM1:
-
Cofactor-associated arginine methyltransferase
- CBP:
-
CREB-binding protein
- CDC6:
-
Cell division cycle-6
- CDK9:
-
Cyclin-dependent kinase-9
- CHIP:
-
Clonal hematopoiesis of indeterminate potential
- CLL:
-
Chronic lymphocytic leukemia
- CN-AML:
-
Cytogenetically normal acute myeloid leukemia
- CR:
-
Complete response
- CRC:
-
Colorectal cancer
- CREB:
-
cAMP-response element binding protein
- DFS:
-
Disease-free survival
- DLBCL:
-
Diffuse large B-cell lymphoma
- DMAP1:
-
DNA methyltransferase associated protein 1
- DNMT1:
-
DNA methyltransferase 1
- DNMT3:
-
DNA methyltransferase 3
- DNMTs:
-
DNA methyltransferase enzymes
- DSBH:
-
Double-stranded helix
- EFS:
-
Event-free survival
- EGFR:
-
Epidermal growth factor receptor
- EMT:
-
Epithelial–mesenchymal transition
- ES:
-
Embryonic stem
- ESCC:
-
Esophageal squamous cell carcinoma
- ESCs:
-
Embryonic stem cells
- EZH:
-
Enhancer of Zeste Homolog
- GBM:
-
Glioblastoma multiforme
- GCB:
-
Germinal center B-cell-like
- GNAT:
-
GCN5-related N-acetyltransferase
- HATs:
-
Histone acetyltransferases
- HBO1:
-
Lysine acetyltransferase 7 or Histone acetyltransferase bound to origin recognition complex 1
- HDAC:
-
Histone deacetylase
- HDLP:
-
Histone deacetylase-like protein
- HDMT:
-
Histone demethylase
- HMTs:
-
Histone methyltransferases
- HPV:
-
Human papilloma virüs
- HSCT:
-
Hematopoietic stem cell transplant
- ICI:
-
Immune checkpoint inhibitor
- IDH:
-
Isocitrate dehydrogenase
- ITD:
-
Internal tandem duplication
- JmJC:
-
Jumonji C
- KAT:
-
Lysine acetyltransferase
- KDM1:
-
Lysine demethylase 1
- KMT:
-
Lysine methyltransferases
- KMT2C:
-
Histone lysine methyltransferase 2C
- LFS:
-
Leukemia-free survival
- LSD1/KDM1A:
-
Lysine-specific demethylase 1A
- MDS:
-
Myelodysplastic syndrome
- MIBC:
-
Muscle-invasive bladder cancer
- MLL:
-
Mixed lineage leukemia
- MORF:
-
MOZ-related factor
- MOZ:
-
Monocytic leukemic zinc finger protein
- ncRNA:
-
Non-coding RNA
- NLS:
-
A nuclear localization sequence
- ORC:
-
Origin recognition complex
- OS:
-
Overall survival
- PADI4:
-
Peptidyl arginine deiminase 4
- PBD:
-
PCNA binding domain
- PBHD:
-
Polybromo homology domain
- PCFBCL:
-
Primary cutaneous follicular B-cell lymphoma
- PCNA:
-
Proliferating cell nuclear antigen
- PD-L1:
-
Programmed death-ligand 1
- PDTC:
-
Poorly differentiated thyroid carcinoma
- PFS:
-
Progression-free survival
- PHD:
-
Plant homeodomain
- PRMT:
-
Arginine methyltransferases
- QM/MM MD:
-
Quantum mechanics/molecular mechanics molecular dynamics
- RFT:
-
Replication foci targeting domain
- SAM:
-
S-adenosyl-l-methionine
- T-ALL:
-
T-cell acute lymphoblastic leukemia
- T-dCyd:
-
4′-Thio-2′ deoxycytidine
- TAF:
-
TATA box-binding protein (TBP)-associated factors
- TBP:
-
TATA box-binding protein (TBP)
- TDG:
-
Thymine DNA glycosylase
- TEs:
-
Transposable elements
- TET:
-
Ten eleven translocation
- TMB:
-
Tumor mutation burden
- TNBC:
-
Triple-negative breast cancer
- TRD:
-
Target recognition domain
- TS:
-
Targeting sequence
- VAF:
-
Variant allele frequency
- VEGF:
-
Vascular endothelial growth factor
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Dalmizrak, A., Dalmizrak, O. (2023). Epigenetic Enzymes and Their Mutations in Cancer. In: Kalkan, R. (eds) Cancer Epigenetics. Epigenetics and Human Health, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-031-42365-9_2
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