Discuss the role of genetic changes in carcinogenesis

Question 1

What are carcinogens?

Answer 1

agents that cause DNA damage, increasing the risk of cancer

Question 2

Which key regulatory systems can DNA mutations disrupt?

Answer 2

• proto-oncogenes
• tumour suppressor genes
• regulators of apoptosis
• genes which regulate interactions between the tumour and its host

Question 3

What do cancer hallmarks determine?

Answer 3

• the natural history of the disease
• its response to various therapies

Question 4

What is the molecular sequence of carcinogenesis ? (4)

Answer 4

1. a molecular change happens in a gene which normally controls cell growth, cell survival or cell senescene
2. these genetic changes overcome normal repair mechanisms and are transmitted to daughter cells
3. natural selection favours the most aggressive clones, leading to ‘progression’
4. mutations and epigenetic alterations give cancer cells cancer hallmarks

Question 5

What is angiogenesis?

Answer 5

the formation of new blood vessels

Question 6

How is apoptosis regulated?

Answer 6

• BCL2 prevents apoptosis by stabilising the mitochondrial membrane
• and blocking the release of cytosome C

Question 7

What role do regulators of apoptosis play in carcinogenesis?

Answer 7

Regulators of apoptosis can cause follicular lymphoma if BCL2 is overexpressed

Question 8

What are 4 general features of benign tumours?

Answer 8

1. remain localised
2. slow growing
3. closely resemble the tissue from which they arise
4. often circumscribed or encapsulated

Question 9

What is hyperchromasia?

Answer 9

When a nucleus looks darker than normal when examined under a microscope

Question 10

What is dysplasia?

Answer 10

• disordered cell growth
• which is a precursor to carcinoma (most common type of cancer)

Question 11

What do regulators of apoptosis do?

Answer 11

stop normal cells from dying but promote apoptosis if DNA damage cannot be repaired

Question 12

What role do oncogenes play in carcinogenesis?

Answer 12

• proto-oncogenes are essential for cell growth and differentiation
• if a mutation happens, a proto-oncogene becomes an oncogene

Question 13

What are 4 general features of malignant tumours?

Answer 13

1. they invade the surrounding tissues and many can metastasise
2. often grow rapidly
3. they vary in their resemblance to the tissue of origin
4. usually have an irregular margin

Question 14

True or false?

Dysplasia is irreversible

Answer 14

False

It is potentially reversible if the stressor is removed

Question 15

What is the role of tumour suppressor genes?

Answer 15

regulate cell growth and prevent tumours from growing

Question 16

What role does telomerase play in carciogenesis?

Answer 16

• Telomeres are bits of DNA which shorten with serial cell division
• Cancers often show up-regulation of telomerase
• Which elongates telomerase

Question 17

What angiogenic factors are produced by some cancers, and what is the reason for it?

Answer 17

• fibroblast growth factor
• vascular endothelial growth factor
• new blood vessel formation is needed for tumour growth

Question 18

What is Knudson’s two-hit hypothesis?

Answer 18

Both alleles of the tumour suppressor gene must be affected by a mutation to cause disease

Question 19

What are 4 genetic features of malignant tumour cells?

Answer 19

1. high nuclear : cytoplasmic ratio
2. nuclear polymorphism and hyperchromasia
3. irregular chromatin distribution
4. irregular nuclear membranes

Question 20

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?

Answer 20

malignant

Question 21

What pathology can follow after a DNA mutation disrupts a regulatory system?

Answer 21

• tumour growth
• invasion of the surrounding tissues
• metastasis

Question 22

What are the 6 main molecular players involved in carciogenesis?

Answer 22

1. regulators of apoptosis
2. tumour suppressor genes
3. angiogenic factors
4. immune system avoidance
5. telomerase
6. oncogenes

Question 23

What are the 6 hallmarks of cancer?

Answer 23

1. sustaining proliferative signalling
2. evading growth suppressors
3. activating invasion and metastasis
4. enabling replicative immortality
5. inducing angiogenesis
6. resisting cell death

Question 24

Cancers can produce factors which switch off the immune system. What is this termed?

Answer 24

immune system avoidance

Question 25

How do cancer cells escape normal growth controls?

Answer 25

• 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

Question 26

What are 4 features of benign tumour cells?

Answer 26

1. low nuclear : cytoplasmic ratio
2. all nuclear of similar size and not hyperchromatic
3. evenly distributed chromatin
4. smooth nuclear membrabes

Question 27

What is neoplasia?

Answer 27

growth that is unregulated, clonal and irreversible

Question 28

What does epigenetic mean?

Answer 28

• 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.

Question 29

How is cancer formation initiated?

Answer 29

by damage to DNA in stem cells which overcomes normal DNA repair mechanisms

Question 30

A tumour closely resembles the tissue from which it arose… Is it most likely benign or malignant?

Answer 30

benign

Question 31

What are 3 examples of carcinogens?

Answer 31

1. chemicals
2. infective agents (HPV etc.)
3. radiation