Pathogenesis of BCC SCC Flashcards
What is the main regulator of G1?
p53
What are the 4 phases of cell cycle
G1, S, G2, M G–>growth S–> synthesize DNA M–> mitosis (prophase, metaphase, ananphase, teleophase)
What is the resting phase?
G0
What are the main proteins that promote cell division
Cyclin
What type of protein is RB?
Tumor suppressor
Which major protein stimulates G1–> S
E2-F
What gene encodes p16
CDKN2A
Do protooncogenes tend to act as dominant or recessive mutations?
Dominant. done through mutation of one allele or amplification (transformation, it gets moved to after the promotor region of a different gene.
3 mechanisms of apoptosis
I. death promoting signals : TNF
II. Lack of growth factors: EGF (EGFR receptors work this way, no signal going through so cell death)
III. DNA damage: UV-induced DNA damage
all pathways increase caspases
What is the major anti-apoptotic protein
BCL2
What is the major pro-apoptotic protein?
BAX
Describe the SHH signaling
Smoothened is a cell surface protein, once it is activated it initiates downstream signaling. Patched is next to it and it is normally inhibiting smoothened. SH binds to patched and makes it remove its inhibition of smoothened. Smoothened then activates GLI which is a factor which increases transcription of GLI, PTCH (gene), BCL2
Where does vismodegib or sonidegib act?
Inhibits activated smoothened. Resistance to this medication occurs with mutations of smoothened
Why do vismodegib/sonidegib cause alopecia?
The transition between hair cycles is controlled by SHH signaling
What type of UV radiation leads to BCC
Intermittentn or intense UV exposure (# of sunburns when younger)
BCC is a tumor of what skin unit?
Pilosebaceous unit –> hence seborrheic distribution
Is there a precancerous lesion to BCC
No, there are no precursor lesions
Why do BCC’s rarely metastasize
They are highly dependent on stromal tissues
What chromosome is PTCH located on?
9 (9 is inverse of P)
What chromosome is p53 located on?
Chr 17
What is the primary risk factor for SCC?
Cumulative lifetime UV radiation
What are the 3 major areas that are higher risk of SCC metastasis?
Lips, genitals, ears (mucous membrane)
Clinical risk factors for SCC metastasis?
Tumor >2cm, poorly differentiated, invasion of subcutaneous fat, perineural invasion, immunosuppression
Verrucous SCC is induced by what HPV types?
HPV-6, 11
What genes are usually mutated in SCC?
p53 m/c TSG mutation/ dysregulated
What is the increase in risk of skin cancer for those with xeroderma pigmentosum?
100x increased risk of skin cancer
What is the mutation in xeroderma pigmentosum?
Defect in nucelotide excision repair (NER) gene
What is the mutation for li-Fraumeni syndrome?
AD, germline mutation with p53 Not much skin cancers
What is the mutation in basal cell nevus syndrome?
AD, gemrline PTCH gene mutaiton.
What occurs in basal cell nevus syndrome?
Odontogenic keratocysts, palmoplantar pits, calcification of falx cerebri, MEDULLOBLASTOMAS, meningiomas, cardiac and ovarian fibromas
What test should you consider with new dx of Gorlins?
MRI for medulloblastomas, also EKG for cardiac fibroma
What is the mechanism of keratinocyte carcinoma related to BRAF inhibitor treatment?
RAS mutations/activation of the MAPK pathway
