DNA DAMAGE, MUTATION AND CANCER Flashcards Preview

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Flashcards in DNA DAMAGE, MUTATION AND CANCER Deck (30)
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1

What is a characteristic of basal cell carcinoma?

They don't metastasize

2

Name 3 types of skin cancer?

- Basal cell carcinoma
- Squamous cell carcinoma
- Malignant melanoma

3

What is a characteristic of squamous cell carcinoma?

They are more invasive

4

What is a characteristic of malignant melanomas?

They are highly metastatic and very invasive

5

What is the mutation signature in skin cancer?

CC >>TT mutations at dipyrimidine sites (CPDs) - these are caused by UV

6

What mutation do skin cancers have?

60% skin cancers at p53 mutations at dipyrimidines

7

Which type of skin cancer has more CC>TT mutations?

SCC has more than BCC

8

What % of XP tumours show a CC>TT mutation?

60%
(90% C>T)

9

What is PTCH1?

It is a transmembrane glycoprotein receptor for hedgehog signalling, involved in control of differentiation and proliferation - not a DNA repair gene

10

In what diseases are PTCH1 mutations found?

73% XP BCCs

11

What is aflatoxin and B1?

Potent liver carcinogen found in moldy rice and peanuts = cancer

12

What does aflatoxin B1 do?

Reacts with guanine, resulting in a G to T transversion mutation (mutation signature for aflatoxin)

13

Describe the pathway for the formation of colon carcinoma

1. Mutation in APC gene (tumour suppressor) = familial polyposis coli

2. Alteration in DNA methylation = changes in gene expression = precarcigenic early adenoma

3. KRAS oncogene mutation = intermediate adenoma

4. DCC mutation = loss of TSG = late adenoma

5. p53 mutation = loss = carcinoma

14

What is lynch syndrome?

Non-polyposis colon carcinoma

15

What characterizes lynch syndrome?

Mismatch repair gene mutations

16

What % of lynch tumours have p53 mutations?

65%

17

What is the mutation signature for lynch syndrome?

C >T at CpG sites

18

Describe 2 mutations that occur in p53 gene in lynch syndrome

1. Cytosine hydrolyses into uracil, which is removed by BER

2. Cytosine methylated at 5 position at CpG sites = 5MeC

5MeC hydrolyses to thymine = G:T mismatch repaired by MMR which is done poorly

So this would lead to transition mutation ( C to T or G to A)

19

What skin diseases don't lead to cancer?

TTD and CS

20

What skin disease has more severe symptoms, CS or XP?

CS

21

What neurological abnormalities does XPA/D/G lead to?

Progressive neurological degeneration

22

What neurological abnormalities does CS and TTD lead to?

Dysmyelination = mental retardation

23

Why does UV have nothing to do with neurological abnormalities in skin disease patients?

Because UV doesn't penetrate into the CNS

24

What do TTD, XPA and CS patients have in common?

Premature ageing

25

What causes premature ageing?

Transcriptional defects = decreased DNA repair

26

What skin disease is most associated with ageing?

CS

27

What skin disease leads to cancer?

XP

28

What skin diseases are most associated with neurological problems and sunburn?

CS and some XPs

29

What skin disease is proficient in TC NER?

XPC, E, V

30

What skin disease is deficient in TC NER and GG NER?

XPA, D, F, G