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
Q

What is a characteristic of basal cell carcinoma?

A

They don’t metastasize

2
Q

Name 3 types of skin cancer?

A
  • Basal cell carcinoma
  • Squamous cell carcinoma
  • Malignant melanoma
3
Q

What is a characteristic of squamous cell carcinoma?

A

They are more invasive

4
Q

What is a characteristic of malignant melanomas?

A

They are highly metastatic and very invasive

5
Q

What is the mutation signature in skin cancer?

A

CC&raquo_space;TT mutations at dipyrimidine sites (CPDs) - these are caused by UV

6
Q

What mutation do skin cancers have?

A

60% skin cancers at p53 mutations at dipyrimidines

7
Q

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

A

SCC has more than BCC

8
Q

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

A

60%

90% C>T

9
Q

What is PTCH1?

A

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

10
Q

In what diseases are PTCH1 mutations found?

A

73% XP BCCs

11
Q

What is aflatoxin and B1?

A

Potent liver carcinogen found in moldy rice and peanuts = cancer

12
Q

What does aflatoxin B1 do?

A

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

13
Q

Describe the pathway for the formation of colon carcinoma

A
  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
Q

What is lynch syndrome?

A

Non-polyposis colon carcinoma

15
Q

What characterizes lynch syndrome?

A

Mismatch repair gene mutations

16
Q

What % of lynch tumours have p53 mutations?

A

65%

17
Q

What is the mutation signature for lynch syndrome?

A

C >T at CpG sites

18
Q

Describe 2 mutations that occur in p53 gene in lynch syndrome

A
  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
Q

What skin diseases don’t lead to cancer?

A

TTD and CS

20
Q

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

A

CS

21
Q

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

A

Progressive neurological degeneration

22
Q

What neurological abnormalities does CS and TTD lead to?

A

Dysmyelination = mental retardation

23
Q

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

A

Because UV doesn’t penetrate into the CNS

24
Q

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

A

Premature ageing

25
Q

What causes premature ageing?

A

Transcriptional defects = decreased DNA repair

26
Q

What skin disease is most associated with ageing?

A

CS

27
Q

What skin disease leads to cancer?

A

XP

28
Q

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

A

CS and some XPs

29
Q

What skin disease is proficient in TC NER?

A

XPC, E, V

30
Q

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

A

XPA, D, F, G