Flashcards in DNA DAMAGE, MUTATION AND CANCER Deck (30)
What is a characteristic of basal cell carcinoma?
They don't metastasize
Name 3 types of skin cancer?
- Basal cell carcinoma
- Squamous cell carcinoma
- Malignant melanoma
What is a characteristic of squamous cell carcinoma?
They are more invasive
What is a characteristic of malignant melanomas?
They are highly metastatic and very invasive
What is the mutation signature in skin cancer?
CC >>TT mutations at dipyrimidine sites (CPDs) - these are caused by UV
What mutation do skin cancers have?
60% skin cancers at p53 mutations at dipyrimidines
Which type of skin cancer has more CC>TT mutations?
SCC has more than BCC
What % of XP tumours show a CC>TT mutation?
What is PTCH1?
It is a transmembrane glycoprotein receptor for hedgehog signalling, involved in control of differentiation and proliferation - not a DNA repair gene
In what diseases are PTCH1 mutations found?
73% XP BCCs
What is aflatoxin and B1?
Potent liver carcinogen found in moldy rice and peanuts = cancer
What does aflatoxin B1 do?
Reacts with guanine, resulting in a G to T transversion mutation (mutation signature for aflatoxin)
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
What is lynch syndrome?
Non-polyposis colon carcinoma
What characterizes lynch syndrome?
Mismatch repair gene mutations
What % of lynch tumours have p53 mutations?
What is the mutation signature for lynch syndrome?
C >T at CpG sites
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)
What skin diseases don't lead to cancer?
TTD and CS
What skin disease has more severe symptoms, CS or XP?
What neurological abnormalities does XPA/D/G lead to?
Progressive neurological degeneration
What neurological abnormalities does CS and TTD lead to?
Dysmyelination = mental retardation
Why does UV have nothing to do with neurological abnormalities in skin disease patients?
Because UV doesn't penetrate into the CNS
What do TTD, XPA and CS patients have in common?
What causes premature ageing?
Transcriptional defects = decreased DNA repair
What skin disease is most associated with ageing?
What skin disease leads to cancer?
What skin diseases are most associated with neurological problems and sunburn?
CS and some XPs
What skin disease is proficient in TC NER?
XPC, E, V