Gene, Mutation and Cancer

Question 1

3 roles of p53

Answer 1

1. Regulate gene expression-key genes involve in growth regulation
2. Facilitates DNA repairs
3. Activates apoptosis of damaged cells

Question 2

Effects of p53
1. DNA strand breaks activates i.____ and ii.____ protein kinases

2. Causes i.____ in p53 blocks degradation, ii.______ number of p53
3. Induction of subset of genes
   i. ___ arrests cell cycle enabling DNA repair
   ii. ___ promotes leakage of iii._____ from mitochondria resulting in iv.____
   v. ____ (Fas) and v._____L_:death receptor and ligand promote vi.______

Answer 2

1i. ATM ii. ATR
2i. Phosphorylation ii. increase
3i. p21 ii. Bax iii. Cytochrome C
iv. Apoptosis v. CD95 vi. apoptosis

Question 3

What is proto-oncogenes?

Answer 3

Genes whose protein products control cell growth and differentiation

Question 4

1. Oncogene are dominant/recessive in action?

2. Mutation of oncogenes activates/deactivates gene expression?

Answer 4

1. Dominant

2. Activates

Question 5

What are the 6 types of mutations?

Answer 5

1. Point mutation (substitution)

Frameshift mutation

2. Insertion
3. Deletion

A section of chromosome

4. Translocation
5. Inversion
6. Amplification

Question 6

Point Mutation (Substitution)

Transition

1. Purine —> Purine/Pyrimidine
2. A—> T/G/C

Transversion

3. Purine—> Purine/Pyrimidine
4. A—> T/G/C

Answer 6

1. Purine
2. G
3. Pyrimidine
4. T/C

Question 7

Point Mutation (Substitution) 
Functional Categorisation

TGT—>TGC
Cys—>Cys

A. Silent Mutation
B. Missense Mutation
C. Nonsense Mutation

Answer 7

A. Silent Mutation

Question 8

Point Mutation (Substitution) 
Functional Categorisation

TGT—>TGG
Cys—>Trp

A. Silent Mutation
B. Missense Mutation
C. Nonsense Mutation

Answer 8

B. Missense Mutation

Question 9

Point Mutation (Substitution) 
Functional Categorisation

TGT—>TGA
Cys—>Stop

A. Silent Mutation
B. Missense Mutation
C. Nonsense Mutation

Answer 9

C. Nonsense Mutation

Question 10

Reciprocal translocation
Eg. t(9;22)(q34;q11)

Robertsonian translocation
Eg. Robertsonian Trisomy 21

What is the differences?

Answer 10

Reciprocal translocation is an exchange of material between nonhomologous chromosomes

Robertsonian translocation is reciprocal translocation which results in one large metacentric chromosome and one extremely small chromosome which may be lost

Question 11

Addition
LTR of retrovirus inserted upstream in control region for proto-oncogene

Which gene is over expressed?

(Long terminal repeats (LTRs) are identical sequences of DNA that repeat hundreds or thousands of times found at either end of retrotransposons or proviral DNA formed by reverse transcription of retroviral RNA.They are used by viruses to insert their genetic material into the host genomes.)

Answer 11

p62, activates mammalian target of rapamycin pathway (mTOR), key regulator of cell growth.

Question 12

Amplification
C-myc gene is constantly expressed in cancer.
What is c-myc gene?

Answer 12

C-myc gene is a central oncogenic switch for oncogenes and the tumour suppressor.

Question 13

Inherited Mutation of cancer genes
Familial cancer after occur at an early stage

BRCA-1

State the 
1.  Syndrome
2. Primary tumour
3. Associates conditions
4. Function of gene products 
of the gene above

Answer 13

1. Familial Breast Cancer
2. Breast Cancer
3. Ovarian Cancer
4. Repair of double strand DNA breaks

Question 14

Inherited Mutation of cancer genes
Familial cancer after occur at an early stage

BRCA-2

State the 
1.  Syndrome
2. Primary tumour
3. Associates conditions
4. Function of gene products 
of the gene above

Answer 14

1. Familial Breast Cancer
2. Breast Cancer
3. Ovarian Cancer, Pancreatic Cancer, Melanoma
4. Repair of double strand DNA breaks

Question 15

Inherited Mutation of cancer genes
Familial cancer after occur at an early stage

p53

State the 
1.  Syndrome
2. Primary tumour
3. Associates conditions
4. Function of gene products 
of the gene above

Answer 15

1. Li-Fraumeni
2. Sarcomas, Breast Cancer
3. Leukaemia, Brain Tumours
4. Transcription factor, Apoptosis, Cell cycle arrest

Question 16

What are the 2 main groups of factors that causes DNA damage?

Answer 16

1. Exogenous (Environmental insult)

2. Endogenous (Carcinogens)

Question 17

Treatment of Breast Cancer

For ER +ve
1.

Answer 17

ER= Oestrogen Receptor

1. Tamoxifen-binds to oestrogen receptor ad block expression of oestrogen- responsive genes

Question 18

Treatment of Breast Cancer

For ER -ve (Chemotherapy)

1. C_____
2. M_____
3. _-f_____

Answer 18

ER= Oestrogen receptor

1. Cyclophosphamide - alkylating agent forms covalent adducts with DNA and enzymes
2. Methotrexate- antifolate binds to the target enzyme dihydrofolate reductase (DHF), increase DHF inhibits purine nucleotide
   and deoxythymidine monophosphate (dTMP syntheses)
3. 5-fluorouracil- forms Fluorodeoxyuridylate (FdUMP) which inhibits thymidylate synthase, FUTP is incorporated into RNA, and *flurodeoxyuridine-5’-triphosphate(FdUTP) is incorporated into DNA

Question 19

What is the effect of oestrogen on cells?

Answer 19

Oestrogen binds to oestrogen receptor, the receptors binds to DNA and cell proliferation is triggered.

Question 20

Oncogenes in Breast Cancer

Hereditary breast cancer constitute 5% of all Breast Cancer

People with Breast Cancer have 85 % chance of getting it while 45% of Familial Breast Cancer (Gene causing) comes from BRCA-2

What are the other causes of Breast Cancer?

Answer 20

Loss of p53
EGF receptors: erbB1,2,3,4 genes, deletion mutation activates to domain
Her-2/Neu: erbB2 gene, receptor (p185) with tyrosine kinase activity

Question 21

Tumour suppressor genes is

1. Dominant/ recessive in action
2. Activated/inactivated when mutated

Answer 21

1. Recessive

2. Inactivated