molecular biology of skin cancer Flashcards
what are the 3 most common skin cancers
- BCC;
- SCC
- cutanous malignant melanoma
what to look for when determining if there is a melanoma
A - asymmetry;
B - boarders;
C - colour (different colours within);
D - diameter;
E - evolving/elevation
what causes skin cancers ( and which ones - 7)
- UV - SCC, BCC, MM;
- ionising radiation - BCC, SCC;
- immunosuppresson - SCC, BCC, MM;
- chronic scarring and ulceration - SCC, BCC;
- wart virus - SCC;
- arsenic - BCC;
- hereditary factors - BCC, MM, SCC
how does UV light cause cancer
UVB radiation causes damge to DNA -> mutations + increases skin sensitivity to sun, thus exacerbating the effect
3 heriditary factors for skin cancer
- germline (familial melanoma);
- acquired mutation (e.g. BRAFv600e);
- epigenetic (e.g. arsenic toxicity)
what protects people from skin cancer (and which types - 5)
- skin pigmentation - MM, SCC, BCC;
- immune system - SCC, BCC, MM;
- DNA repair - MM, SCC, BCC;
- accurate control of cell division;
- behaviour (avoiding UV, wearing SPF)
what are the gene mutations seen in BCCs (4)
germline - MC1R, PTCH1, PTCH2;
acquired - PTCH1, PTCH2, RASA1
what pathway is disrupted in BCCs
hedgehog pathway - PTCH1/2 codes for a receptor in this pathway
what is the hedgehog pathway
a pathway involved in cell differentiation and proliferation
smoothened molecule promotes cell division while patched inhibits smoothened singalling -> (sonic) hedgehog molecule binds to patched to that it can’t inhibit smoothened (cell division occurs)
what happens if there is a fault in smoothened or patched (hedgehog pathway)
if there is a fault in patched - cant fully control smoothened => proliferation;
if there is a fault in smoothened - can’t be fully controlled by patched => proliferation
what drug can block smoothened
Vismodegib
what pathway does RASA1
MAP-kinase (RAS molecule)
MAP kinase pathway
receptor TKa recieves signal -> RAS (may go via RET first) -> BRAF -> MEK ->ERK –(into cell nucleus)–> activates TFs -> promotes cell differentiation, proliferation and survival
what is Gorlin’s syndrome
PCTH1 mutation - multiple BCCs at an early stage
what are pre-cancerous conditions (in skin)
conditions that can lead to SCCs - solar keritosis (Actinic keratosis) and Bowen’s disease
solar keratosis appearance
appearance varies - A flat or thickened papule/plaque;
White or yellow; scaly, warty, or horny surface;
Skin coloured, red, or pigmented;
Tender or asymptomatic
what is another name for bowen’s disease
squaemous cell carcinoma in situ
what mutations are associated w SCCs
germline - MC1R; OCA1/2; XP; p53; RASA1 etc.
acquried - p53, RASA1
what other condition does OCA1/2 mutation cause
Oculocutaneous albinism - reduction or complete lack of melanin pigment in the skin, hair and eyes -> white hair, pale skin and poor vision (slightly better vision and less pale if OCA2 is the one affected)
what does XP (xeroderma pigmentosum) mutation result in and why
increased sun burn, freckles, blistering after going in the sun - due to defect of the enzyme system that repairs DNA after damage from ultraviolet rays
what does p53 do
tumour suppressor gene - guardian of the genome; halts the cell cycle to allow for DNA repair and can induce apop in cells if damage is too bad
gene mutations associated with malignant melanoma
gerlimine - MC1R; CDNK2A; Rb; BRCA2; XP mutations; p53;
acquired - p53; RASA1; BRAF; cKIT
what syndrome is CDKN2A/CDK4 associated with
atypical naevus syndrome - presents with many moles
what is BRAF mutation associated with
superficial spreading and nodular melanoma
what does cKIT code for and what is a mutation associated with
tyrosine kinase receptors - acral+mucosal melanoma
what is vemurafenib
monoclonal antibody that inhibits BRAF production - stops cells proliferating
what are the 2 mutations that cause the majority of melanomas
BRAF; BRAFV600E
