The Molecular basis of cancer 3 Flashcards
What do tumour suppressor genes do?
prevent rapid cell cycling, thereby rapid cell division and growth.
control critical checkpoints in the cell cycle etc.
What type of mutations can lead to cancer from tumour suppressor genes?
loss of function (inactivating) mutations.
How many copies of the gene does the mutation have to be in for tumour suppressor genes?
both. recessive. two hit hypothesis.
What happens if one gene is mutated for tumour suppressor genes?
slight cell cycle progression advantage. one mutated gene can increase the chances of the second copy becoming mutated.
What is retinablastoma?
rare childhood tumour of the retina (neural precursor cells of the retina)
how many children are affected by Rb?
1/20,000
How many forms of the disease are there?
hereditary, sporadic.
Features of hereditary RB?
-every cell has the mutation.
-develops at a young age.
-tumours in both eyes,
-mutant Rb allele on chromosome 13 in every cell of the body.
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Features of sporadic RB?
- chromosomal changes only in tumour cells.
- develops at a later age
- one tumour in one eye.
- born with 2 healthy copies, but sustain a loss of function mutation.
what does rb gene do?
regulatory cell cycle progression.
What phase entrance does rb control?
S phase entrance. cannot enter until it is ready to do so,
What does acquisition of the p53 mutations do?
allows tumour to evade the apoptotic cel death pathways, thereby promoting proliferation.
How many tumours show mutations and loss of function of p53?
50%.
what specific cell responses does p53 include?
cell cycle arrest, senescence, cell differentiation, apoptosis.
what boundary does p53 halt cycle at?
G1/S.
What is p53?
a transcription factor.
what protein is p53 sequestered by?
MDM2. it is held in an inactive form.
When is p53 upregulated?
when the cell halts at the G1/S boundary and there is DNA damage.
What genes does p53 induce the transcription of?
p21.
What is p21?
a cyclin dependant kinase inhibitor, thus preventing the cell from moving into S phase.
What is an example of a human cancer where p53 is lost early in cancer development?
Skin cancer (squamous cell carcinoma SCC)
How many SCC’s is p53 gene mutated in?
90%.
What mutation do SCC’s have?
C to T base substitution.
What do MMR genes do?
repair DNA if errors during DNA replication occur.
how many mmr genes do humans have?
8 (msh, mlh, pms)
How do mmr genes work (formation wise)?
as dimers - so they pair up.
How many genes of mmr must be mutated for effect?
both. 2 hit hypothesis.
What cancers have defects in these genes?
sporadic and hereditary colorectal cancers.
Hereditary Non-polyposis colorectal cancer (HNPCC) - loss of mismatch repair genes.
- leech syndrome.
- inherited, so around 2-3% of all inherited cancers.
- loss of MSH gene in one copy in every cell in the body.
- reasonably high penetrance. (80%).
