Cancer epigenetics Flashcards
What is the definition of definition of epigenetics?
Heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence
What are the 3 general features of epigenetics?
- Responds to the environment (internal and external)
- Reversible/plastic
- Heritable: cell to cell, mother to child and transgenerational
What are the biological processes in which epigenetics is involved?
• DNA repair
• DNA replication
• Recombination
• Transcriptional gene regulation
• Chromosome segregation
• Proliferation
• Imprinting
• X-inactivation
• Self-renewal/differentiation/development
• CANCER (tumour suppressors, oncogenes, clonal evolution, etc.)
=> Any process where DNA accessibility needs to be regulated
How do epigenetics induce their modifications?
- Histone modifications
- Chromatin remodeling and organization
- Histone variants
- DNA methylation
- Non-coding RNA
=> All these epigenetic modifications are changed in cancer
What are 4 ways to define epigenetic regulation?
Cooperative, redundant, reversible and cell type specific
Do all epigenetic regulations have the same role if they act on the same DNA region?
No, they can act on the same DNA region but have different functions depending on the cell type
=> Cell type specific
How can epigenetic regulations organize chromatin (2 ways)?
Methylation: compact DNA
Acetylation: readable DNA
Do epigenetic regulations change the DNA?
Epigenetic transcriptional regulation occur WITHOUT changes of DNA and is heritable
Do epigenetic regulations play a role in cancer?
Yes, epigenetic mechanisms contribute to each classic hallmark of cancer
Are transcriptional deregulation of epigenetic factors common in cancer?
Yes:
• transcriptional deregulation of various epigenetic enzymes is very common in tumors
• consequently, most if not all tumors display altered epigenetic landscape
Is epigenetics causing cell transformation, or rather the consequence of it?
The answer is likely to be a mix of both, but several epigenetic factors have been shown to contribute to tumorigenesis
Why is cancer considered as an epigenetic disease?
• Cancer cell genomes undergoes dramatic changes in the epigenetic pattern
• Epigenetic silencing of tumor suppressor genes
• Involved in important oncogenic processes as DNA repair, apoptosis, and drug detoxification
• Hyper-methylation, -deacetylation and the concomitant
underexpression of transcription regulators, regulators of apoptosis, and cell signaling genes
How do epigenetics play a role in cancer cell transformation?
They stop the differentiation of cells => immortal proliferating cells that do not differentiate into their mature post-mitotic state
Why is epigenetics important in tumorigenesis at 4 different levels?
- Activation of oncogenes, inactivation of tumor suppressor genes
- Contribute to clonal advantage/provide the cell with selective advantages that promote tumor progression
- Involved in cellular processes contributing to tumorigenesis or development of cancer (e.g. malignant self-renewal, differentiation blockade, evasion of cell death, and tissue invasiveness)
- Provide cellular plasticity and allow cell extrinsic/environmental cues to cancer cells
What is clonal evolution and heterogeneity of cancer in regards to epigenetics?
Clonal evolution: cell clones with the most optimal survival and proliferative advantages
Epigenetics alterations contribute to clonal evolution and tumor heterogeneity but also allow response to external stimuli
Clonal evolution and high epigenetic mutations (higher than DNA mutations) make it much more difficult to treat cancer patients => adds complexity and treatment resistances
