5a: Genetic Pathways In Cancer Flashcards
(46 cards)
Fill in the blanks:
As neoplasia progresses through _____ lesions, the number of mutation acquired by the lesion _____.
1) Precursor
2) increases
Fill in the blanks:
Selective advantage ensures that _____ acquisition is broadly _____
1) Mutation
2) Consistent
What is oncogene co-operation
Where mutations are more likely to be selected based on interactions with previous mutations, allowing oncogenes to co-operate to ensure a positive advtange for the tumour
Which mutation does KRAS often co-occur with?
PIK3CA
What is example of two mutations that co-occur in pancreatic cancers but not often in lung?
KRAS and TP53
Why may pair of mutations co-occur in one tumour but not another?
The context/areas of the tumours are different, therefore co-occurrence may give a select advantage in one but not the other, depending on the tissue types.
Give an example of a mutation that is selected against in endometrial cancers with MSI?
TGFRBR2, due to its repeat sequences
Fill in the blanks:
Mutations may select against other mutations.
It is unlikely two mutations will activate the same _____. This will lead to _____ _____.
1) Pathway
2 & 3) mutual exclusion
Which 3 mutations are mutually exclusive in the MAPK signalling pathway?
EGFR, KRAS, BRAF
Fill in the blanks:
If a mutation is essential, it is an example of oncogene ______.
If a mutation is not essential, it is an example of oncogene ______.
1) addiction
2) amnesia
What are the 3 genetic pathways of colorectal cancer?
- Chromosomal instability (CIN)
- Microsatellite instability (MSI)
- Chromosome and microsatellite stable
Why is CpG Island Methylator Phenotype colorectal cancer not considered its own genetic pathway despite being well described?
Due to its close link to the MSI pathway
Most sporadic CRCs arise as a result of which mutation?
APC
Which signalling pathway does APC activate?
Wnt signalling
Fill in the blanks:
Approximately __% of sporadic CRC tumours will arise _____ to the _____ _____ (left sided)
1) 70
2) distal
3 & 4) splenic flexure
What % of sporadic tumours will show MSI
10-15%
When does MSI occur?
When there is a failure of the mismatch repair function
What des MSI result in?
Hypermutation/ increased mutation rate
What is ‘redundancy’ in regards to the genome?
If there is a dysfunctional protein, other similar proteins may act to take over the same role.
What are the protein pairs that make up the complex in the DNA mismatch repair pathway?
- MSH2 & MSH6
- MLH1 & PMS2
What causes almost all cases of MSI in sporadic CRC tumours?
MLH1 promoter methylation
Fill in the blanks:
MSH2/_____ dimers and _____/PMS2 _____ function to excise_____ _____.
1) MSH6
2) MLH1
3) dimers
4 & 5) mismatched bases
How many of the proteins in the complexes in mismatch repair must be lost in order for the repair to fail?
Just 1
Will repeats be added/deleted if a loop occurs on the:
- template strand
- newly synthesised strand
- Repeats deleted
- Repeats added
