Tumour Suppressors Flashcards
(52 cards)
What is a tumour suppressor? (1)
A gene that protects a cell from one or more steps on the path to cancer
What is a tumour suppressor? (2)
A gene which, when mutated, predisposes an individual to cancer
What are the 3 classes of TSGs?
Gatekeepers
Caretakers
Landscapers
What do gatekeeper TSGs do?
Prevent growth of potential cancer cells
What do caretaker TSGs do?
Maintain the integrity of the genome
What do landscaper TSGs do?
Control the cellular microenvironment
What are the 10 hallmarks of cancer?
Resisting cell death Avoiding immune destruction Enabling replicative immortality Evading growth suppressors Sustaining proliferative signalling Genome instability and mutation Inducing angiogenesis Activating invasion and metastasis Tumour-promoting inflammation Deregulating cellular energetics
What 2 kinds of retinoblastoma are there?
Familial (40%) and sporadic (20%)
When do familial retinoblastomas appear compared to sporadic?
At a younger age
Where can familial retinoblastomas develop?
Often in both eyes, can also be accompanied by tumours in other organs
What was Knudson’s two-hit hypothesis?
Cancer is a multi-hit disease i.e. it is the result of accumulated mutations.
Why does a familial mutant Rb allele mean the carrier will develop bilateral disease much earlier than in sporadic case?
The first somatic mutation in a familial Rb mutation case leads to two mutant Rb gene copies. The chances of this happening on both sides is much higher. In sporadic cases, 2 somatic mutations must occur to reach the same stage.
Name the 7 ways of eliminating normal Rb function
- Non-disjunction (Chromosome)
- Non-disjunction and replication
- Mitotic recombination
- Gene conversion
- Deletion
- Point mutation
- Promoter methylation
Name 2 key tumour suppressor genes
p53
PTEN
How was p53 originally identified?
By its interaction with viral proteins
SV40, Adenovirus and Papillomavirus
What do p53 mutations do?
Some don’t stop cancer developing, some actively help cancer develop.
What proportion of human cancers is p53 mutated in?
~50%
What happens in the majority of cancers that don’t have p53 mutations?
There are other mutations that affect the p53 activation pathway or other indirect ways to inactivate p53.
In which rare, autosommal dominant condition do patients have a germline TP53 mutation?
Li-Fraumeni Syndrome - develops early and aggressively
What is the protein structure of p53?
Nuclear phosphoprotein. Acts in tetrameric form.
What is the function of p53?
Transcription factor that recognises a 10bp consensus sequence in promoters
Where are p53 mutations clustered?
Exons 5-8
Where are the p53 mutation hotspot?
Amino acids 175, 248, and 273 - DNA binding domains.
What do mutant p53 do to normal p53?
Interfere with normal p53 function.
