Cancer epigenetic Flashcards
What is tumourigenesis
Tumourigenesis comprises multiple steps of mutations in
cancer driver genes that provide the cell with a selective growth advantage over its neighbouring cells.
What is cancer?
A genetic disease at a cellular level
What causes cancer initiaition?
Accumulating genetic alterations and epigenetic
dysregulation
How can epigenetic alterations influence aspects of cancer?
Influence: expression of oncogenes and tumour suppressor genes and signal transduction, resulting in enhanced cancer growth, invasion and metastasis.
What are the steps of the multistep model of tumourigenesis?
Initiation, promotion, progression and metastasis
What is initiation?
involves the alteration, change, or mutation of genes arising spontaneously or induced by exposure to a carcinogenic agent.
What is promotion?
Relatively lengthy and reversible process in which actively proliferating preneoplastic cells accumulate.
What is progression?
It is the final stage of neoplastic transformation, where genetic and phenotypic changes and cell proliferation occur.
What is metastasis?
It involves the spread of cancer cells from the primary site to other parts of the body through the bloodstream or the lymph system.
What are the hallmarks of cancer?
- Escaping growth suppression
- Activating invasion and metastasis
- Sustained proliferative signalling
- Avoiding destruction by the immune system
- Inflammations that can promote tumours
- Genome instability and mutations
- Inducing angiogenesis
- Unlimited replication
- Deregulation of cellular energy
- Resisting cell death
What are the DNA methylation changes detected in cancer cells?
- Gene specific hypo- and hyper-methylation
- Global hypomethylation across the genome (detected in all cancers)
- Increase incidence of mutations
what is global hypomethylation?
Hypomethylation of repetitive regions across the genome which causes genomic instability
what is the link between altered epigenetic tags and genetic changes?
methylatiomn gives rise to spontaneous mutation by converting cytosine into thymine
What are the epigenetic changes in cancer?
- Overall global level of methylation decreases
- Gene specific hypermethylation at CpG islands located within the promoter region of genes increase
- Increase in altered histone modification profiles.
What are cancer stem cells?
Drug-resistant cells (resistant to classic chemotherapy drugs) within tumours with capabilities of self-renewal, differentiation and tumourigenicity when transplanted
