Cancer (L18) Flashcards
What is a germline mutation?
A mutation in a cell that goes on to make gametes, passed on to next generation
What is a somatic mutation, and what can it lead to?
Mutation in in other cells (not gametes), cannot be passed on, lead to cancer
What signals to cancer cells no longer respond (well) to?
many of the signals that control cellular growth and death
What is metastasis? When does it occur?
In late stages, cells break through normal tissue boundaries and metastasise (spread) to new sites in the body
The more times a cell divides, the more likely it is to…
develop a mutation
The likelihood of mutation increases with the number of times a cell has…
divided
Why does cancer risk increase with age?
Cancer is the result of an accumulation of mutations, hence why risk of cancer increases with age
What causes mutations?
Mutations may be spontaneous (occur by chance) or the result of exposure to a mutagen (also called carcinogen)
What do tumour suppressor genes normally encode?
proteins that normally prevent uncontrolled cell growth e.g.
○ proteins that inhibit cell division
○ prevent other mutations (= DNA repair enzymes)
What happens when tumour suppressor genes are down regulated?
cell growth i.e. recessive mutation -> cancer
What is the process of sending a signal for cell division?
(external) signal for transcription -> unbinding of tumour suppressor genes -> release of transcription factor -> nucleus -> cell division genes expressed
What type mutation in tumour suppressor genes usually leads to cancer?
loss of function mutation
What is an onco-gene?
A gene which encodes proteins that promote cell growth e.g. proteins that stimulate cell division
Normal function = to produce cell growth
What type of mutation in an onco-gene typically leads to cancer?
Dominant mutations (gain of function)
What happens if we are missing a tf that represses transcription?
Loss of regulation = expressed at wrong time/place = more growth-stimulating protein = more cell division (at wrong time/place)
What happens if there is a mutation in the region of the gene which encodes regulation? (rather than in transcripted region effecting folding)
Proteins have sequence where recognised by protease. If mutation here, protein isn’t recognised by protease so isn’t degraded in response to signal ending cell division = proteins for cell division expressed for longer/active all the time
What are the 3 ways that an onco gene leads to increased cell growth?
- By loss of regulation (e.g. missing the tf that represses transcription) leading to more growth-stimulating protein
- Mutation in regulatory region of gene, leading to protein always active or not degraded (expressed for longer)
- Gene duplication - accidental over-replication may lead to expression in other parts of the cell = protein made/expressed too much
Describe ‘leukemia’
A group of blood cancers resulting in high numbers of abnormal cells (not fully developed blood cells called blasts/leukaemia cells)
What is a clinical condition/example of how oncogene and tumour suppressor mutations lead to cancer?
Chronic Myeloid Leukaemia
Describe the mutation that causes Chronic Myeloid Leukaemia
- Translocation leading to oncogene BRC-ABL (chromosome 9 and 22
= new gene that is a little of BRC gene and mostly ABL gene so under the wrong regulatory sequence = too much of weird protein all the time
How is the ABL protein normally turned on?
ABL protein normally needs cell signal to be activated and produce tf that turns on cell division
What happen to ABL activation with mutation?
With translocation, always on, can always activate tf, doesn’t need cell signal
Why doesn’t one wrong thing or one mutation necessarily lead to cancer
Because multiple transcription factors are needed to control replication of a gene and .: cell replication/division
So what 3 things need to happen to make cancerous cells?
1x oncogene = accelerator
○ DOMINANT mutation = gain of function = growth signals = uncontrolled growth
2x loss of function mutations in the same tumour suppressor gene
○ RECESSIVE mutation = loss of function predisposes you to cancer
What are possible treatments for cancer?
- Surgery to remove cells
○ Especially if early on - Radiation therapy
○ Targeted to tumour - Chemotherapy
○ Chemicals that result in less components for DNA replication = inhibits cell replication
