Physiology: Photocarcinogenesis Flashcards
Define oncogene
Overactive form of a gene that positively regulates cell division - drives tumour formation when activity or copy number is increased (accelerator)
What is clonal evolution?
The accumulation of a series of cell mutations in successive generations
Which skin cancers are associated with intermittent burning episodes of sun exposure?
Melanoma and BCC
Which form of UV radiation can penetrate through window glass?
UVA
Which form of UV radiation causes sunburn?
UVB
What is vemurafenib?
BRAF inhibitor
Which skin cancer is associated with life-time cumulative UV exposure?
SCC
Which form of UV radiation causes indirect oxidative damage?
UVA
How does UVA cause skin ageing?
Penetrates deeper into the skin (than UVB) and damages the elastic fibres of collagen
Which form of UV radiation penetrates to the Earth’s surface only when the sun is directly overhead?
UVB
Almost all BCC are related to activation of which signalling pathway?
Hedgehog
How can you reduce resistance to vemurafenib?
Add a MEK inhibitor
Define proto-oncogene
The normal, not yet mutated form of an oncogene
What is SMO?
Oncogene involved in the Hedgehog signalling pathway - implicated in BCC
What is vismodegib?
Targeted treatment for some BCCs which binds to SMO
Which form of UV radiation causes direct DNA damage?
UVB
What is the mutation caused by UVB?
CC → TT UV signature mutation
How are CPDs and 6-4PPs usually repaired?
Nucleotide excision repair
How is 8-oxo-dG normally repaired?
Base excision repair
Define photoaging
Premature ageing of the skin caused by repeated exposure to UV radiation
What is the mutation caused by UVA?
C → A point mutation
Which form of UV radiation causes pigmentation and skin ageing?
UVA
What is PTCH?
Tumour suppressor involved in the Hedgehog signalling pathway - implicated in BCC
How does UV radiation affect the immune system?
Leads to immunosuppression
How does UVA cause indirect DNA damage?
Oxidation of deoxyguanosine (dG) to form 8-oxo-deoxyguanosine (8-oxo-dG) which (if not repaired) causes a C → A point mutation
What are immune checkpoint inhibitors?
Targeted cancer treatment which stop immune checkpoints from inhibiting T-cell activation, so allows an improved immune response to the cancer
How does UVB cause direct DNA damage?
UVB leads to the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4), which (if not repaired) cause a CC → TT UV signature mutation
40-60% of melanomas have what mutation?
BRAF
Define tumour suppressor
A gene that negatively regulates regulates cell division to prevent the formation of a tumour when functioning normally e.g. p53
Which skin type is the most sensitive to sun?
Fair skin type
Define cancer
An accumulation of abnormal cells that multiply through uncontrolled cell division and spread to other parts of the body by invasion and/or distant metastasis via the blood and lymphatic system
