Physiology: Photocarcinogenesis

Question 1

Define oncogene

Answer 1

Overactive form of a gene that positively regulates cell division - drives tumour formation when activity or copy number is increased (accelerator)

Question 2

What is clonal evolution?

Answer 2

The accumulation of a series of cell mutations in successive generations

Question 3

Which skin cancers are associated with intermittent burning episodes of sun exposure?

Answer 3

Melanoma and BCC

Question 4

Which form of UV radiation can penetrate through window glass?

Answer 4

UVA

Question 5

Which form of UV radiation causes sunburn?

Answer 5

UVB

Question 6

What is vemurafenib?

Answer 6

BRAF inhibitor

Question 7

Which skin cancer is associated with life-time cumulative UV exposure?

Answer 7

SCC

Question 8

Which form of UV radiation causes indirect oxidative damage?

Answer 8

UVA

Question 9

How does UVA cause skin ageing?

Answer 9

Penetrates deeper into the skin (than UVB) and damages the elastic fibres of collagen

Question 10

Which form of UV radiation penetrates to the Earth’s surface only when the sun is directly overhead?

Answer 10

UVB

Question 11

Almost all BCC are related to activation of which signalling pathway?

Answer 11

Hedgehog

Question 12

How can you reduce resistance to vemurafenib?

Answer 12

Add a MEK inhibitor

Question 13

Define proto-oncogene

Answer 13

The normal, not yet mutated form of an oncogene

Question 14

What is SMO?

Answer 14

Oncogene involved in the Hedgehog signalling pathway - implicated in BCC

Question 15

What is vismodegib?

Answer 15

Targeted treatment for some BCCs which binds to SMO

Question 16

Which form of UV radiation causes direct DNA damage?

Answer 16

UVB

Question 17

What is the mutation caused by UVB?

Answer 17

CC → TT UV signature mutation

Question 18

How are CPDs and 6-4PPs usually repaired?

Answer 18

Nucleotide excision repair

Question 19

How is 8-oxo-dG normally repaired?

Answer 19

Base excision repair

Question 20

Define photoaging

Answer 20

Premature ageing of the skin caused by repeated exposure to UV radiation

Question 21

What is the mutation caused by UVA?

Answer 21

C → A point mutation

Question 22

Which form of UV radiation causes pigmentation and skin ageing?

Answer 22

UVA

Question 23

What is PTCH?

Answer 23

Tumour suppressor involved in the Hedgehog signalling pathway - implicated in BCC

Question 24

How does UV radiation affect the immune system?

Answer 24

Leads to immunosuppression

Question 25

How does UVA cause indirect DNA damage?

Answer 25

Oxidation of deoxyguanosine (dG) to form 8-oxo-deoxyguanosine (8-oxo-dG) which (if not repaired) causes a C → A point mutation

Question 26

What are immune checkpoint inhibitors?

Answer 26

Targeted cancer treatment which stop immune checkpoints from inhibiting T-cell activation, so allows an improved immune response to the cancer

Question 27

How does UVB cause direct DNA damage?

Answer 27

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

Question 28

40-60% of melanomas have what mutation?

Answer 28

BRAF

Question 29

Define tumour suppressor

Answer 29

A gene that negatively regulates regulates cell division to prevent the formation of a tumour when functioning normally e.g. p53

Question 30

Which skin type is the most sensitive to sun?

Answer 30

Fair skin type

Question 31

Define cancer

Answer 31

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