Molecular basis of cancer Flashcards
What are driver mutations
Mutations that do affect function of genes that regulated:
- Proliferation
- APoptosis
- Immortality
What are passenger mutations
All other mutations that are no relevant to the promotion of cancer
What leads to the gain of function of a gene
Overexpression: amplification/regulatory regions change
Point mutations/fusions
What leads to the loss of function of a gene
Point mutation, deletion-frameshift, loss of allele
how does retinoblastoma arise
Tumour arises in precursors of photoreceptor cells
How is retinoblastoma treated
Radiotherapy or surgery
What are sporadic causes of retinoblastoma
Unilateral
What are familial causes of retinoblastoma
BIlateral
What is the 2 hit hypothesis
familial tumours due to a single random somatic event
Sporadic tumours require two random somatic events
-ie if you have one functioning copy of the tumour suppressor gene you’re okay. If the other gets affected the cell becomes hyper proliferative. Odds of having 2 mutations is very low. However if you inherit 1 then the odds of having another mutation in the other then its very likely that you will get cancer
What is the phenotype of the mutant Rb gene like in retinoblastoma
Dominant at the level of the whole organism
What is the phenotype of the mutant allele like in retinoblastoma
Recessive at the cellular level
Why is the second mutation very common
Because you get loss of heterozygosity where the tumour is
The one that is damaged usually replaces the good copy of the gene because sometimes in mitosis, there is crossing over so you will get a bad gene in 1 in 4 cells
What are the checkpoints in the cell cycle
R
G1
G2
M
What does the ‘R’ checkpoint check
Cell requires growth signals to pass this checkpoint
What happens at the G1 checkpoint
DNA damage checkpoint, entrance to S blocked if DNA is damaged
