Cancer- A genetic disease

Question 1

What are the changes that occurs as a result of mutation in oncogenes?

Answer 1

1. Change amount of products synthesised (overexpression)
2. Change in type of produce (Inactive > active)
3. Decrease inhibition of housekeeping genes

Question 2

What are the types of oncogene mutations? One example each

Answer 2

1. Point mutation

eg. Ras:
glycine (12) > valine
Glycine (61) > ??)

2. Chromosomal rearrangements (translocation)

eg. c-myc
t(8:14)(q24;q32)
- moved to a strong Ig promoter gene
Burkitt’s lymphoma

eg. bcl2 t(14:18)
Leukkaemias, Non-Hodgkin lymphoma, Solid tumours

3. Gene amplification
   eg. HER2
   Breast cancer

Question 3

List the types of spontaneous DNA damage that can occur

Answer 3

1. DNA polymerase error/proofreading error
2. Deamination- C can be deaminated to form U (.’. transcription error)
3. Depurination (deletion of N- base)- Purine (A or G) cleaved
4. Depyrimidation
5. Oxidation

Question 4

List the types of carcinogenic DNA damage that can occur

Answer 4

1. Endogenous- require metabolic activation of carcinogen

2. Exogenous- direct environmental effect

Question 5

Give example of 2 endogenous carcinogen

Answer 5

1. Polycyclic aromatic hydrocarbons (Smoking)

= eg. Benzopyrene (BP), oxidised in epithelium of lung > cytochrome p450 > BPDE (carcinogen)

2. Alcohol

Question 6

Name 3 exogenous carcinogen

Answer 6

X-ray/radiation

reactive oxygen species

chemical mutagens

virus and infectious agents (HBV, HepB/C- liver cancer
EBV- lymphoma, nose/throat cancer
HPV- cervical cancer)

Question 7

What phase of the cell cycle can damage happen? And what are the results from it?

Answer 7

S-phase replication error

Wrong complementary bases

Question 8

When does spontaneous DNA damage happen? What is affected?

Answer 8

S-/G1/G2 phases

movement of transposable elements (transposers)

Question 9

What is a way to remove dimers?

Answer 9

Nucleotide excision repair

excision nuclease cut off parts of the strand (~12bp)

helicase, DNA polymerase & DNA ligase makes new strand

Question 10

Give an example of a nucleotide excision repair gene mutation

Answer 10

Xeroderma pigmentosum

XPA gene

defect in human nucleotide excision repair

symptoms:
- light sensitive,
- increase risk of sunlight 
 induce cancer,
- neurological abnormality (increase rate of oxidative metabolites in neurons)

Question 11

What are the possible mutations in prostate cancer? What gene is affected?

Answer 11

Androgen receptor mutation

Single point mutations > substitutions/premature stop codon

Nucleotide insertions and deletions > frameshift

Complete/partial deletion

Intronic mutations > AR RNA splicing