Neoplasia 3

Question 1

What do oncogenes do?

Answer 1

Turn up genes that promote growth

Question 2

What do tumour suppressor genes do?

Answer 2

Turn off genes that slow growth

Question 3

What are the 4 NORMAL classes of regulatory genes?

Answer 3

Oncogenes
Tumour Suppressor genes
Genes that regulate programmed cell death (i.e apoptosis)
Genes involved in DNA repair

Question 4

Where is the APC mutation commonly seen?

Answer 4

Colon Cancer (FAP)

Question 5

What are the 3 key concepts?

Answer 5

Initiation
Progression
Persistance

Question 6

What is adenoma?

Answer 6

Dysplastic lesion of glandular epithelium

Question 7

What are the 3 categories of growth receptors?

Answer 7

Receptors with intrinsic tyrosine kinase activity
7 Transmembrane G protein Couple Receptors
receptors without intrinsic tyrosine kinase activity

Question 8

What is the most commonly mutated photo-oncogene in tumours?

Answer 8

RAS

Question 9

How does the mutation of RAS lead to unchecked signalling?

Answer 9

Mutations block the hydrolysis of GTP to GDP

Question 10

Describe Myc?

Answer 10

One of the last points in the sequence.
Its a nuclear transcription factor that promotes growth
Common in lymphoma
Burkett lymphoma t(8;14) - Myc translocation which is diagnostic

Question 11

Describe PI3K?

Answer 11

Most commonly mutated kinase in cancer.

Question 12

Describe 7 transmembrane G protein?

Answer 12

G protein coupled receptors are responsible for a wide range of physiological responses
Often targets of pharmacological agents
Can be involved in cancers

Question 13

Describe non - intrinsic TK receptors?

Answer 13

They can’t autophosphorylate – recruit something else to do it for them

Question 14

Describe tumour suppressor genes?

Answer 14

They are lots of proteins which can inhibit the cell cycle

They are often prefixed with a ‘p’ like p53 and p16

Question 15

Describe p53?

Answer 15

It is the most commonly mutated protein across all cancers

Question 16

Describe what p53 does?

Answer 16

It senses DNA abnormalities at G1 and pauses the cell cycle. It increases levels of p21 which is a CDK inhibitor.
CDK is activated by cyclins.
If the DNA is repaired p53 restarts the cell cycle, if the repair is not possible p53 imitates apoptosis (via the BAX pathway)

Question 17

What does PTEN do?

Answer 17

Increases transcription of p27.
P27 blocks CDKs and cell cycle progression
Remember CDK are activated by cyclins
Inhibits PI3K/AKT pathway we saw earlier
Without PTEN and therefore p27 cells can proliferate in an uncontrolled fashion

Question 18

Name some DNA repair genes?

Answer 18

MLH1 MLH2 PMS1 PMS2

Question 19

What are the BRCA genes?

Answer 19

They are commonly mutated in breast cancers BRCA 1 and 2

Question 20

Describe BCL2

Answer 20

It is anti-apoptotic

Intrinsic pathway win mitochondria

Question 21

What chromosome would you find Bcl2?

Answer 21

Chromosome 18