Epigenetic modulators, modifiers and mediators in cancer aetiology and progression
- PMID: 26972587
- PMCID: PMC4888057
- DOI: 10.1038/nrg.2016.13
Epigenetic modulators, modifiers and mediators in cancer aetiology and progression
Abstract
This year is the tenth anniversary of the publication in this journal of a model suggesting the existence of 'tumour progenitor genes'. These genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, and thus cause altered differentiation throughout tumour evolution. The past decade of discovery in cancer epigenetics has revealed a number of similarities between cancer genes and stem cell reprogramming genes, widespread mutations in epigenetic regulators, and the part played by chromatin structure in cellular plasticity in both development and cancer. In the light of these discoveries, we suggest here a framework for cancer epigenetics involving three types of genes: 'epigenetic mediators', corresponding to the tumour progenitor genes suggested earlier; 'epigenetic modifiers' of the mediators, which are frequently mutated in cancer; and 'epigenetic modulators' upstream of the modifiers, which are responsive to changes in the cellular environment and often linked to the nuclear architecture. We suggest that this classification is helpful in framing new diagnostic and therapeutic approaches to cancer.
Conflict of interest statement
The authors declare competing interests : see Web version for details.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4888057/bin/nihms787058f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4888057/bin/nihms787058f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4888057/bin/nihms787058f3.gif)
Similar articles
-
Regulatory roles of epigenetic modulators, modifiers and mediators in lung cancer.Semin Cancer Biol. 2017 Feb;42:4-12. doi: 10.1016/j.semcancer.2016.11.007. Epub 2016 Nov 10. Semin Cancer Biol. 2017. Retraction in: Semin Cancer Biol. 2019 Feb;54:183. doi: 10.1016/j.semcancer.2018.11.011. PMID: 27840279 Retracted. Review.
-
The epigenetic progenitor origin of human cancer.Nat Rev Genet. 2006 Jan;7(1):21-33. doi: 10.1038/nrg1748. Nat Rev Genet. 2006. PMID: 16369569 Review.
-
The role of mutations in epigenetic regulators in myeloid malignancies.Immunol Rev. 2015 Jan;263(1):22-35. doi: 10.1111/imr.12246. Immunol Rev. 2015. PMID: 25510269 Review.
-
Epigenetic Determinants of Cancer.Cold Spring Harb Perspect Biol. 2016 Sep 1;8(9):a019505. doi: 10.1101/cshperspect.a019505. Cold Spring Harb Perspect Biol. 2016. PMID: 27194046 Free PMC article. Review.
-
Cellular reprogramming and cancer development.Int J Cancer. 2013 Mar 15;132(6):1240-8. doi: 10.1002/ijc.27963. Epub 2012 Dec 17. Int J Cancer. 2013. PMID: 23180619 Review.
Cited by
-
A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer's Disease Risk in Older Men with Prostate Cancer.Degener Neurol Neuromuscul Dis. 2024 May 17;14:33-46. doi: 10.2147/DNND.S445130. eCollection 2024. Degener Neurol Neuromuscul Dis. 2024. PMID: 38774717 Free PMC article. Review.
-
Multiomics approach towards characterization of tumor cell plasticity and its significance in precision and personalized medicine.Cancer Metastasis Rev. 2024 May 18. doi: 10.1007/s10555-024-10190-x. Online ahead of print. Cancer Metastasis Rev. 2024. PMID: 38761231 Review.
-
A Review on Picrosides Targeting NFκB and its Proteins for Treatment of Breast Cancer.Cell Biochem Biophys. 2024 May 9. doi: 10.1007/s12013-024-01281-1. Online ahead of print. Cell Biochem Biophys. 2024. PMID: 38724755 Review.
-
Transient loss of Polycomb components induces an epigenetic cancer fate.Nature. 2024 May;629(8012):688-696. doi: 10.1038/s41586-024-07328-w. Epub 2024 Apr 24. Nature. 2024. PMID: 38658752 Free PMC article.
-
Tumours form without genetic mutations.Nature. 2024 May;629(8012):534-535. doi: 10.1038/d41586-024-01019-2. Nature. 2024. PMID: 38658714 No abstract available.
References
-
- Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet. 2006;7:21–33. This is the model suggesting that some genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, causing altered differentiation throughout tumour evolution; the current Review revisits this model. - PubMed
-
- Versteege I, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394:203–206. - PubMed
-
- Mack SC, et al. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature. 2014;506:445–450. This paper reported an absence of recurrent mutations in a subtype of paediatric posterior fossa ependymoma, suggesting the existence of alternative, non-mutational mechanisms for cancer initiation. - PMC - PubMed
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous