Pathogenesis of BCC SCC

Question 1

What is the main regulator of G1?

Answer 1

p53

Question 2

What are the 4 phases of cell cycle

Answer 2

G1, S, G2, M G–>growth S–> synthesize DNA M–> mitosis (prophase, metaphase, ananphase, teleophase)

Question 3

What is the resting phase?

Answer 3

G0

Question 4

What are the main proteins that promote cell division

Answer 4

Cyclin

Question 5

What type of protein is RB?

Answer 5

Tumor suppressor

Question 6

Which major protein stimulates G1–> S

Answer 6

E2-F

Question 7

What gene encodes p16

Answer 7

CDKN2A

Question 8

Do protooncogenes tend to act as dominant or recessive mutations?

Answer 8

Dominant. done through mutation of one allele or amplification (transformation, it gets moved to after the promotor region of a different gene.

Question 9

3 mechanisms of apoptosis

Answer 9

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

Question 10

What is the major anti-apoptotic protein

Answer 10

BCL2

Question 11

What is the major pro-apoptotic protein?

Answer 11

BAX

Question 12

Describe the SHH signaling

Answer 12

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

Question 13

Where does vismodegib or sonidegib act?

Answer 13

Inhibits activated smoothened. Resistance to this medication occurs with mutations of smoothened

Question 14

Why do vismodegib/sonidegib cause alopecia?

Answer 14

The transition between hair cycles is controlled by SHH signaling

Question 15

What type of UV radiation leads to BCC

Answer 15

Intermittentn or intense UV exposure (# of sunburns when younger)

Question 16

BCC is a tumor of what skin unit?

Answer 16

Pilosebaceous unit –> hence seborrheic distribution

Question 17

Is there a precancerous lesion to BCC

Answer 17

No, there are no precursor lesions

Question 18

Why do BCC’s rarely metastasize

Answer 18

They are highly dependent on stromal tissues

Question 19

What chromosome is PTCH located on?

Answer 19

9 (9 is inverse of P)

Question 20

What chromosome is p53 located on?

Answer 20

Chr 17

Question 21

What is the primary risk factor for SCC?

Answer 21

Cumulative lifetime UV radiation

Question 22

What are the 3 major areas that are higher risk of SCC metastasis?

Answer 22

Lips, genitals, ears (mucous membrane)

Question 23

Clinical risk factors for SCC metastasis?

Answer 23

Tumor >2cm, poorly differentiated, invasion of subcutaneous fat, perineural invasion, immunosuppression

Question 24

Verrucous SCC is induced by what HPV types?

Answer 24

HPV-6, 11

Question 25

What genes are usually mutated in SCC?

Answer 25

p53 m/c TSG mutation/ dysregulated

Question 26

What is the increase in risk of skin cancer for those with xeroderma pigmentosum?

Answer 26

100x increased risk of skin cancer

Question 27

What is the mutation in xeroderma pigmentosum?

Answer 27

Defect in nucelotide excision repair (NER) gene

Question 28

What is the mutation for li-Fraumeni syndrome?

Answer 28

AD, germline mutation with p53 Not much skin cancers

Question 29

What is the mutation in basal cell nevus syndrome?

Answer 29

AD, gemrline PTCH gene mutaiton.

Question 30

What occurs in basal cell nevus syndrome?

Answer 30

Odontogenic keratocysts, palmoplantar pits, calcification of falx cerebri, MEDULLOBLASTOMAS, meningiomas, cardiac and ovarian fibromas

Question 31

What test should you consider with new dx of Gorlins?

Answer 31

MRI for medulloblastomas, also EKG for cardiac fibroma

Question 32

What is the mechanism of keratinocyte carcinoma related to BRAF inhibitor treatment?

Answer 32

RAS mutations/activation of the MAPK pathway