Skin cancers 2 Flashcards
What are the most common DNA mutations caused by UV?
C–>T
What is signature 7 associated with?
Large numbers of CC–>TT dinucleotide mutations at di-pyrimidines
First step of forming a TT from a CC?
UV hits DNA and forms covalent links between neighbouring pyrimidine nucleotides
What occurs as a result of covalent links forming between neighbouring pyrimidine nucleotides?
Cause a kink in the DNA structure
What happens to the covalently linked neighbouring pyrimidine nucleotides?
They can be repaired with a photolyase enzyme, or via transcription coupled nucleotide exscision
What is unique ab the photolyase enzyme?
It is UV inducible
What happens when the covalently linked neighbouring pyrimidine nucleotides are not repaired?
Stalling of the DNA replication fork
How do cells move past stalling of the DNA replication fork?
Specialised polymerases
What is a specialised polymerase used to move past stalling of the DNA replication fork?
Trans-lesion polymerase
What does trans-lesion polymerase do?
Gives the cell extra time to repair DNA damage before the replicase returns to complete replication
Issue with trans-lesion polymerase?
It is error prone
How does the trans-lesion polymerase enable the replication fork to move past the bulky pyrimidine dimers?
It inserts two other dinucleotides–> two As
THis would then lead to the two Ts being in the place of the two Cs
Where does cSCC primarily occur?
Sun-exposed body parts
What % of keratinocyte cancer deaths does cSCC cause?
75%
Which groups of people are at greater risk of developing cSCC?
Significant cumulative ultraviolet light exposure (near equator/work outdoors)
People more susceptible to sunburn (low pigmentation)
Immunosuppressed people
Hereditary skin conditions
Why do people with lighter skin have more risk of developing skin cancer?
Less melanocytes to shield the nuclei of the keratinocytes
What are some hereditary skin conditions that make people more susceptible to cSCC?
albinism
xeroderma pigmentosum
What does a cSCC look like?
scaly or crusty raised area of skin with a red, inflamed base.
What happens to the dermal compartment in cSCC?
it is infiltrated by cutaneous squamous cell carcinomas–> tumor cells
cSCC cellular properties?
cSCC cells are enlarged and have more abundant cytoplasm and they have vesicular nuclei (nuclei have vesicles within them)
What is seen in cSCC?
Keratin pearly
What are keratin pearls?
cyst like structures, which have basal like proliferative cells outside them
What is in they cysts in keratin pearls?
densely packed layers of terminally differentiated cells going towards the middle from the outside in
What surrounds keratin pears?
Basal-like proliferative cells
What is the result of a well differentiated cSCC?
better prognosis and a reduced change of metastasis
What is absent in a poorly differentiated cSCC?
Keratin pearls are completely absent
Non-UV causes of cSCC?
Chemical carcinogens–> coal tar
What does coal tar and soot contain?
DMBA (DIMETHYLBENZ(A)ANTHACENE)
How was a multi stage skin carcinogen model induced in mice?
Painted the back skin of mice with DMBA and TPA (tumor promoter)
What does the correct combination of DMBA and TPA induce?
Hyperproliferation and a hyperplastic epidermis
What is a papilloma?
A benign epidermal tumour
