Oncogenes

Question 1

What are oncogenes derivatives of?

Answer 1

Proto-oncogenes

Question 2

Are oncogene mutations dominant or negative?

Answer 2

Dominant - only one allele needs to be mutated

Question 3

What are oncogenes?

Answer 3

Positive regulators of cell growth and proliferation

Question 4

What stages in the pathway to proliferation are a potential target for oncogenic transformation?

Answer 4

Growth factors
Growth factor receptors
Signal transducers
Nuclear proteins, transcription factors and coactivators

Question 5

Mechanisms of mutations for an oncogene

Answer 5

Point mutations/ deletion 
Chromosomal amplification 
Chromosomal translocation 
Retroviral insertion 
Retroviral transduction

Question 6

Are tumour suppressor genes dominant or negative?

Answer 6

Negative

Question 7

2 examples of oncogenes which are caused by deletion or point mutations

Answer 7

Ras

Raf

Question 8

2 examples of oncogenes which are caused by gene amplification

Answer 8

Abl

Myc

Question 9

Example of an oncogene which are caused by chromosomal rearrangement - inset an enhancer

Answer 9

Ig enhancer: Myc

Question 10

What is the chromosomal rearrangement required to produce the Ig enhancer Myc?

Answer 10

t[8:14]

Question 11

Example of an oncogene which are caused by chromosomal rearrangement - gene fusion

Answer 11

BCR:Abl

Question 12

What is the chromosomal rearrangement required to produce BCR:Abl

Answer 12

t[9:22]

Question 13

What does gene fusion cause?

Answer 13

Excessive production of hyperactive fusion protein in the cell

Question 14

Give an example of a virus which is inserted into a chromosome to induce insertional mutagenesis

Answer 14

ALV

Question 15

3 examples of oncogenes which are caused by retroviral transduction

Answer 15

Ras
Abl
ErbB2

Question 16

What causes activation of Ras in cancer making it constitutively active?

Answer 16

Viruses

Mutations

Question 17

What are the 3 forms of Ras

Answer 17

H-
Ki-
N-

Question 18

When is Ras normally activated in a cell?

Answer 18

When it is bound to GTP

Question 19

What are the effectors of Ras?

Answer 19

MAPK pathway
PI3K pathway
Rac
Ral

Question 20

How do you activate Ras?

Answer 20

Mutations at 12, 13 and 61 - constitutive Ras activation

NF1 deletion - no GAP to convert it back to RasGDP

Question 21

What is NF1?

Answer 21

Neurofibromin
negative regulator of Ras
GAP- GTPase activator protein

Question 22

What are the 3 forms of Raf?

Answer 22

A-
B-
C-

Question 23

What causes activation of Raf in cancer making it constitutively active?

Answer 23

Viruses

Mutations

Question 24

What is Raf?

Answer 24

A serine/threonine kinase

Question 25

What is the most common Raf mutation?

Answer 25

V600E (85% of mutations)

Question 26

What domain is Raf commonly mutated?

Answer 26

Clustered kinase domain

Question 27

What causes activation of c-Abl in cancer making it constitutively active?

Answer 27

Viruses Mutations Chromosomal translocations

Question 28

What is Abl?

Answer 28

a tyrosine kinase

Question 29

What is the philadelphia chromosome?

Answer 29

t[9:22]

Question 30

What disease is associated with Abl mutations?

Answer 30

Leukaemias

Question 31

How is Abl inactive in normal cells?

Answer 31

The N-terminal cap covers the active site of the catalytic domain

Question 32

Why is Abl active in tumour cells?

Answer 32

The N-terminal cap is changed to BCR and therefore does not inhibit the active site of the catalytic domain

Question 33

What causes activation of EGFR in cancer making it constitutively active?

Answer 33

viruses | mutations

Question 34

what is EGFR?

Answer 34

A receptor tyrosine kinase

Question 35

How is EGFR overactivated?

Answer 35

Mutated so it does not need EGF | EGF is overexpressed so EGFR is always saturated

Question 36

Where s c-Myc located?

Answer 36

Nucleus

Question 37

What causes activation of c-Myc in cancer making it constitutively active?

Answer 37

Chromosomal translocation

Question 38

What cancer is associated with c-Myc?

Answer 38

Burkitt lymphoma

Question 39

What is c-Myc

Answer 39

a transcription factor | also regulates translation

Question 40

How does Myc promote cell cycle progression?

Answer 40

Binds to MAX as a heterodimer binds to the promoter of target genes activates cyclins promote cell cycle progression

Question 41

Why is c-Myc only generally a cell proliferation promoter?

Answer 41

If it is injected into a fibroblast without serum, it will stimulate apoptosis

Question 42

Give an example drug treatment for BCR:Abl, how it works and for what disease

Answer 42

Gleevac Structural deregulation of the kinase domain in BCR-Abl by binding to it Chronic myeloid leukaemia

Question 43

Give 2 examples drug treatment for EGFR, how it works and for what disease

Answer 43

Getfitinib Binds to the active site and blocks it in EGFR ErbB2 Non-small cell lung cancer, and other cancers Herceptin Ab against the EGF binding site Currently in clinical use, so no specific cancer