6a: Mutations In Cancer Flashcards
1
Q
Why is aberrant Wnt signaling so detrimental?
A
It has effects on many downstream signalling molecules which can affect all hallmarks of cancer
2
Q
What 2 types of functions can mutations cause?
A
- Gain of function: excessive normal or new function
- Loss of function: inability to perform normal function
3
Q
Are oncogenes gain or loss of function?
A
Gain
4
Q
Where may Gain of Function mutations arise from?
A
- changes in sequence resulting in a constitutively active form of the protein
- increases in levels of normal protein
- novel fusion protein
5
Q
How many hits do GOF mutations usually require?
A
One
6
Q
Briefly outline the normal KRAS pathway
A
- GTP binds and activates KRAS
- KRAS-GTP activates the RAF-MAPK pathway
- RAS-GAP hydrolyses GTP>GDP, inactivating KRAS, and its downstream signalling
- RAS-GEF removes ADP from KRAS, and the cycle can continue
7
Q
Briefly outline the mutated pathway of KRAS
A
- KRAS binds to GTP, activating KRAS
- There is a protein confirmation change in KRAS, meaning RAS-GAP cannot hydrolyse the GTP, so KRAS is constantly activated.
- This in turn means the downstream pathway is constantly activated
8
Q
Is KRAS an oncogene or tumour suppressor gene?
A
Oncogene, it has a gain of function when mutated
9
Q
Are tumoursuppressors loss or gain of function?
A
Loss
10
Q
What may Loss of Function arise from?
A
- Changes in sequence resulting in an altered non-functional form of the protein
- Decrease in the levels of normal protein
11
Q
How many hits so LOF mutations normally have?
A
2
