Tumour Pathology 5

Question 1

How do tumour suppressor genes function?

Answer 1

Discourage cell growth
Temporarily halt cell division to carry out DNA repair

Question 2

What is an anti-oncogene?

Answer 2

Tumour suppressor gene

Responsible for:
Apoptosis
DNA repair
Negative regulation of mitosis

Question 3

What do mutations in retinoblastoma gene cause?

Answer 3

Favour cell proliferation - anti-oncogene (tumour suppressor gene)

Question 4

What is the inherited form of oncogenesis?

Answer 4

One defective copy of RB gene
Somatic point mutation of other copy

Question 5

What is the sporadic form of oncogenesis?

(no previous history or genetic defect)

Answer 5

Both hits occur in a single cell

Question 6

What portion of cancers are hereditary?

Answer 6

5-10% of all cancers

Question 7

Give two examples of inherited cancer syndromes?

Answer 7

Familial retinoblastomas
Familial adenomatous polyposis of colon

Question 8

What gene is responsible for signal transduction and also FAP colon cancer?

Answer 8

APC

Question 9

What gene is responsible for cell cycle regulation and causes retinoblastoma and osteosarcomas?

Answer 9

Rb

Question 10

Which gene is responsible for DNA repair and causes breast and ovarian cancer?

Answer 10

BRCA 1/2

Question 11

How does HER2 contribute to breast cancer

Answer 11

Tyrosine kinase receptors
Inactive growth factor receptor, receptors come together when GF binds
Mutation causes over expression of HER2
Receptor can bind more GF

Question 12

How does BRAF contribute to melanoma

Answer 12

BRAF signal transducer
Proto-oncogene
Mutation creates BRAF V600
BRAF V600 always active, pushes cell cycle forward
(sunlight)

Question 13

How can retinoblastoma gene contribute to malignancy of the eye

Answer 13

Hereditary mutation cause one gene to stop producing protein
Another mutation can cause remaining protein to loose function
E2F released, progression of cell cycle, no regulation

Question 14

How can a mismatch pair contribute to colon cancer

Answer 14

MLH1 and other genes recognise and replace damaged DNA
MLH1 mutation reduces amount of p53, decrease mismatch repair, mismatch remains
DNA replication accumulates mutations

Question 15

How does p53 have a role in numerous cancers

Answer 15

Mutation - loss of p53 function
No longer stops cell cycle at checkpoints if there is damage

Question 16

How can smocking cause cancer

Answer 16

Numerous chemicals in cigarette smoke
Metabolised to carcinogens in liver
Released into circulation
Damages DNA
Numerous mutations eg mutations in p53

Question 17

How can Human papilloma virus cause cancer

Answer 17

Infection of cervix
Produces E6 protein which binds and inactivates p53
Increased risk of subsequent uncontrolled cell division, precancer then cancer

Question 18

How can Alcohol cause cancer

Answer 18

Large amounts converted to acetylaldehyde
Goes in systemic circulation
Cause double stranded breakdown of DNA in many genes
Increase cancer risk

Question 19

Give examples of oncoprotein products

Answer 19

Growth factors
Growth factor receptors
Proteins involved in signal transduction
Nuclear regulatory proteins
Cell cycle regulators

Question 20

What is c-myc

Answer 20

Increase proteins that drive cell cycle
Increase proteins that stop cell death
Proto-oncogene

Question 21

How can c-myc promote cancer

Answer 21

Translocation - c-myc gene breaks off chromosome, attaches to different one
In B cell can bind beside immunoglobulin regulatory sequence
Huge increase in c-myc