Melanoma

Question 1

Where can malnocytes be found?

Answer 1

Skin
Hair follicles
Basal layer of epidermis
Inner ear 
Meninges

Question 2

How is melanin released?

Answer 2

Melanocytes which sit the basal layer throw out dendrites pass melanin to melanosomes which cap nuclei and protect them from uv damage

Question 3

What are the benign and malignant tumours of melanocytes?

Answer 3

Benign - melanocytic naevus

Malignant - melanoma

Question 4

Treatment of melanoma?

Answer 4

Primary tumour - excised

Regional lymph node disease - lymph node excision or sentinel lymph node biopsy

Disseminated disease

• chemo
• immune therapy
• molecular targets
• palliative care

Question 5

What does immune therapy in melanoma do?

Answer 5

Maintains T cell activation

Question 6

What does Breslow’s depth measure?

Answer 6

The length of the tumour

Measure form the granular layer

Question 7

Who is more prone to melanoma?

Answer 7

MM RISK
Moles
Moles - dysplastic type 
Red hair/freckles/blue eyes
Inability to tan (burn easily)
Sunburn
Kindred (family history)

Question 8

What macroscopic features are used to help diagnosis of melanoma?

Answer 8

Major features
-change in size, colour or shape

Minor features

• inflammation
• bleeding/crusting
• sensory change
• lesion diameter of 7mm or greater

Question 9

What is the ABCDE for mole changes?

Answer 9

Asymmetry
Borders
Colour
Diameter 
Evolution

Question 10

List the hallmarks of cancer

Answer 10

Evade apoptosis
Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Tissue invasion and metastasis 
Sustained angiogenesis
Limitless replicative potential

Question 11

What normally happens in the MAPK pathway?

Answer 11

Ligand binds to receptor
Activates Ras causing a signalling cascade via Raf
Proliferation by upregulation of cyclin D and CDK so cell is pushed into cell cycle

Question 12

How do melanoma cells achieve self-sufficiency in growth signals?

Answer 12

Get NRas mutations
Braf mutations
These activate the MAPK pathway

Question 13

How is melanoma with a BRAF mutation treated?

Answer 13

BRAF inhibitor

Question 14

How do melanoma cells gain insensitivity to anti-growth signals?

Answer 14

Deletion of CDKN2A
This normally codes for two cyclin-dependent kinase inhibitors which normally cause for oncogene-induced senescence when oncogenes are activated

Question 15

Why can a mutation to BRAF/NRas not necessarily cause cancer?

Answer 15

Because cyclin-dependent kinase inhibitors normally stop progression through the cell cycle when oncogenes are activated

Naevi often have Bras/BRAF mutations but CDKN2A induces senescence

Question 16

What are one of the two proteins that CDK2NA codes for? What is its function?

Answer 16

P14ARF - increases p53 activity

Question 17

What does activation of the AKT pathway result in?

Answer 17

Evasion of apoptosis

Question 18

What controls activation/suppression of the AKT pathway?

Answer 18

Activation

• activated by NRas and MAPK pathway
• PTEN encodes a protein which suppresses it (so loss of PTEN can activate it)

Question 19

How do melanoma cells alter their adhesion to metastasise?

Answer 19

Switch from E-cadherin to N-cadherin

• E-cadherin promotes binding between melanocytes
• N-cadherin promotes binding between melanocytes and fibroblasts as they invade into the stroma

Increased expression of αV-β3
-aids stromal invasion and proteolysis

Question 20

Why do chromosomes have telomeres?

Answer 20

Prevent end-to-end fusion that would lead to chromosomal abnormalities
Provide a buffer zone to protect the flanking DNA sequences from being eroded because DNA replication leads to chromosome shortening on the leading strand

Question 21

What is replicative senescence?

Answer 21

Protects the telomeres from becoming so short that flanking DNA gets damaged and could get chromosomal end-to-end fusions
Due to up-regulation of cyclin-dependent kinase inhibitors eg p16 which cause permanent exit from the cell cycle

Question 22

Give an example of oncogene-induced senescence in melanoma

Answer 22

Cyclin-dependent kinase inhibitors such as p16 and p21 induce senescence if there is an NRas/BRAF mutation activating the MAPK pathway

Question 23

How do cancer cells gain limitless replicative potential in melanoma?

Answer 23

Cancer cells lack cyclin-dependent kinase inhibitors eg p21 and p16
Cells reach crisis where telomeres have shortened so much so get chromosomal fusions leading cell death
Some cell clones survive due to rewctivation if telomerase, which can synthesis new telomeres

Question 24

How do breast cancers produce self-sufficient growth signals?

Answer 24

HER2 gene amplification

Question 25

Where are melanocytes derived from?

Answer 25

Neural crest cells which migrate to many places