Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis
Abstract
:1. Introduction: Epigenetics, Differentiation, and Testicular Germ Cell Tumors
2. Testicular Germ Cell Tumors Type II
2.1. Pathology
2.2. Tumorigenesis
2.3. Cytogenetics
2.4. Genetics
3. Epigenetics and TGCT
3.1. Tumorigenesis
3.2. DNA Methylations
3.3. Histone Modifications and Modulations
3.4. Driver Genes
3.5. Epidrugs and TGCT
4. iPSC in Oncology
4.1. TGCT
4.2. Other Malignancies
5. Perspectives and Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AFP | alfa fetoprotein |
5-aza | 5-azacytidine |
5-aza-cD | 5-aza-2′-deoxycytidine |
BEP | bleomycin, etoposide, and (cis)platin |
bromodomaini | bromodomain inhibitor |
CC | choriocarcinoma |
CDK | cyclin D kinase |
CDKi | CDK inhibitor |
CYT | spermatocyte |
DNMT | DNA methyltransferase |
DATECA | the Danish testis cancer study group |
DNMT | DNA methyl transferase |
DNMTi | DNA methyltransferase inhibitor |
EC | embryonal carcinoma |
EGFR | epidermal growth factor receptor |
ESC | embryonic stem cells |
EZH2 | enhancer of Zeste-2 |
EZH2i | EZH2 inhibitor |
GCNIS | germ cell neoplasia in situ |
GON | gonocytes |
HAT | histone acetylase |
hCG | human chorionic gonadotropin |
HDAC | histone deacetylase |
HDACi | histone deacetylase inhibitor |
HDMT | histone demethylase |
HMT | histone methyltransferase |
iPSC | induced pluri- to totipotent stem cells |
KDM | lysine demethylase |
KDMi | lysine demethylase inhibitor |
Kme | methylated histone 3 lysine |
LDH | Lactate dehydrogenase |
LSD1i | LSD1 inhibitor |
5mC | 5-methyl cytosine |
5mhC | 5-methylhydroxy cytosine |
MGCT | microinvasive germ cell tumor |
NGC | normal germ cells |
NSCLC | non-small cell lung cancer |
NST | non-seminomatous germ cell tumor |
OCT4 | the protein of POU5F1 |
OSKM | the OCT4, SOX2, KLF4, and MYC panel |
OSLN | the OCT4, SOX2, LIN28, and NANOG panel |
PGC | primordial germ cells |
PRC2 | polycomb repressor complex 2 |
SCLC | small cell lung cancer |
SCEC | small cell esophageal cancer |
SE | seminoma |
SPA | spermatogonia type A |
SPB | spermatogonia type B |
TER | teratoma |
TET | DNA demethylase |
TGCA | The Genomic Cancer Atlas |
TKI | tyrosine kinase inhibitor |
TNM | international tumor, nodes, and metastases classification |
TSS | transcription start site. |
WHO | World Health Organization |
YST | yolk sac tumor |
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Expressed Transcription Factors | Histologic Types | NGC | GCNIS | SE | EC | TER | |
---|---|---|---|---|---|---|---|
Epigenetic mediators | High | PRAME LDHC | PRAME, KIT, SOX17, NANOG | PRAME, KIT, SOX17, KLF4 POU5F1, NANOG, MYC | NANOG, POU5F1, DNMT3B | RB1, MYC | |
Low | RB1 | RB1 | RB1, MYC | POU5F1, SO)X2, LIN28, NANOG | |||
5mC | +++ | Neg | Neg/++ | +++ | |||
5mhC | Neg | Neg | +++ | ||||
Epigenetic modifiers | H2A.Z | +/+++ | +++ | Neg/+ | Neg/+ | ||
H3K4 | Me1 +++ Me2/me3 ++ | Me1/me2/me3 +++ | Me1 ++/+++ | Me1 neg/+ Me2/Me3++/+++ | |||
H3K9me1/me2 | Neg/+ | ++ | ++ | ||||
H3K9ac | +++ | Neg/+ | Neg/+ | ||||
H3K27me2 | |||||||
H3K27me3 | +++ | Ac/+ | +++ | neg | |||
Epigenetic modulators | DNMT | Low | High | ||||
TET | Low | High | low | ||||
HMT | EZD2 | +++ | Neg/+ | neg | |||
HDMT | UTX | Neg | Neg | Neg | Neg | ||
JMJDD3 | Neg/+ | Neg | Neg/+ | Neg/+ | |||
HAT | High | Low | |||||
HDAC | Low | High |
Pharmacologic Group | Drugs | TGCT | Ref | Other Malignancies | |
---|---|---|---|---|---|
Studies | Indications | ||||
Cell lines | Patients | ||||
DNMTi | 5-aza | X | X | Myelodysplastic syndromes | |
5-aza-cD | X | X | |||
Guadecitabine | X | ||||
KDMi | Chaertocin | [141] | |||
JIB-04 | [141] | ||||
EZH2i | Tazemetostat | Follicular NH lymphoma | |||
Bromodomaini | JQ11 | X | [143] | ||
LSD1i | CBB3001 | X | |||
HDACi | belinostat | X | [144] | Cutaneous T cell lymphoma | |
chicamide | X | ||||
depsipeptide | X | [144] | |||
panobinostat | X | [144] | Cutaneous T cell lymphoma | ||
Romidepsin | X | Cutaneous T cell lymphoma | |||
Quisinostat | X | [141] | |||
trichostatin | |||||
vorinostat | X | ||||
CDKi | dinaciclib | [140] | |||
Flavo-piridol | [140] | ||||
NVP-2 | [140] | ||||
SY0351 | [140] | ||||
thal-sns-032 | [140] | ||||
THZ1 | [140] | ||||
THZ531 | [140] | ||||
YKL-5-214 | [140] |
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von Eyben, F.E.; Kristiansen, K.; Kapp, D.S.; Hu, R.; Preda, O.; Nogales, F.F. Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis. Int. J. Mol. Sci. 2023, 24, 4148. https://doi.org/10.3390/ijms24044148
von Eyben FE, Kristiansen K, Kapp DS, Hu R, Preda O, Nogales FF. Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis. International Journal of Molecular Sciences. 2023; 24(4):4148. https://doi.org/10.3390/ijms24044148
Chicago/Turabian Stylevon Eyben, Finn E., Karsten Kristiansen, Daniel S. Kapp, Rong Hu, Ovidiu Preda, and Francisco F. Nogales. 2023. "Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis" International Journal of Molecular Sciences 24, no. 4: 4148. https://doi.org/10.3390/ijms24044148