Discuss the role of genetic changes in carcinogenesis Flashcards
What are carcinogens?
agents that cause DNA damage, increasing the risk of cancer
Which key regulatory systems can DNA mutations disrupt?
- proto-oncogenes
- tumour suppressor genes
- regulators of apoptosis
- genes which regulate interactions between the tumour and its host
What do cancer hallmarks determine?
- the natural history of the disease
- its response to various therapies
What is the molecular sequence of carcinogenesis ? (4)
- a molecular change happens in a gene which normally controls cell growth, cell survival or cell senescene
- these genetic changes overcome normal repair mechanisms and are transmitted to daughter cells
- natural selection favours the most aggressive clones, leading to ‘progression’
- mutations and epigenetic alterations give cancer cells cancer hallmarks
What is angiogenesis?
the formation of new blood vessels
How is apoptosis regulated?
- BCL2 prevents apoptosis by stabilising the mitochondrial membrane
- and blocking the release of cytosome C
What role do regulators of apoptosis play in carcinogenesis?
Regulators of apoptosis can cause follicular lymphoma if BCL2 is overexpressed
What are 4 general features of benign tumours?
- remain localised
- slow growing
- closely resemble the tissue from which they arise
- often circumscribed or encapsulated
What is hyperchromasia?
When a nucleus looks darker than normal when examined under a microscope
What is dysplasia?
- disordered cell growth
- which is a precursor to carcinoma (most common type of cancer)
What do regulators of apoptosis do?
stop normal cells from dying but promote apoptosis if DNA damage cannot be repaired
What role do oncogenes play in carcinogenesis?
- proto-oncogenes are essential for cell growth and differentiation
- if a mutation happens, a proto-oncogene becomes an oncogene
What are 4 general features of malignant tumours?
- they invade the surrounding tissues and many can metastasise
- often grow rapidly
- they vary in their resemblance to the tissue of origin
- usually have an irregular margin
True or false?
Dysplasia is irreversible
False
It is potentially reversible if the stressor is removed
What is the role of tumour suppressor genes?
regulate cell growth and prevent tumours from growing
What role does telomerase play in carciogenesis?
- Telomeres are bits of DNA which shorten with serial cell division
- Cancers often show up-regulation of telomerase
- Which elongates telomerase
What angiogenic factors are produced by some cancers, and what is the reason for it?
- fibroblast growth factor
- vascular endothelial growth factor
- new blood vessel formation is needed for tumour growth
What is Knudson’s two-hit hypothesis?
Both alleles of the tumour suppressor gene must be affected by a mutation to cause disease
What are 4 genetic features of malignant tumour cells?
- high nuclear : cytoplasmic ratio
- nuclear polymorphism and hyperchromasia
- irregular chromatin distribution
- irregular nuclear membranes
Under a microscope, you can see that a cell has a high nuclear : cytoplasmic ratio. Is this a malignant tumour cell or a benign tumour cell?
malignant
What pathology can follow after a DNA mutation disrupts a regulatory system?
- tumour growth
- invasion of the surrounding tissues
- metastasis
What are the 6 main molecular players involved in carciogenesis?
- regulators of apoptosis
- tumour suppressor genes
- angiogenic factors
- immune system avoidance
- telomerase
- oncogenes
What are the 6 hallmarks of cancer?
- sustaining proliferative signalling
- evading growth suppressors
- activating invasion and metastasis
- enabling replicative immortality
- inducing angiogenesis
- resisting cell death
Cancers can produce factors which switch off the immune system. What is this termed?
immune system avoidance
How do cancer cells escape normal growth controls?
- By developing mutations which convert proto-oncogenes into oncogenes
- These oncogenes encode oncoproteins which promote cell growth even in the absence of normal growth-promoting signals
What are 4 features of benign tumour cells?
- low nuclear : cytoplasmic ratio
- all nuclear of similar size and not hyperchromatic
- evenly distributed chromatin
- smooth nuclear membrabes
What is neoplasia?
growth that is unregulated, clonal and irreversible
What does epigenetic mean?
- how your behaviors and environment can cause changes that affect the way your genes work.
- Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence.
How is cancer formation initiated?
by damage to DNA in stem cells which overcomes normal DNA repair mechanisms
A tumour closely resembles the tissue from which it arose… Is it most likely benign or malignant?
benign
What are 3 examples of carcinogens?
- chemicals
- infective agents (HPV etc.)
- radiation
