Melanoma Flashcards
Where can malnocytes be found?
Skin Hair follicles Basal layer of epidermis Inner ear Meninges
How is melanin released?
Melanocytes which sit the basal layer throw out dendrites pass melanin to melanosomes which cap nuclei and protect them from uv damage
What are the benign and malignant tumours of melanocytes?
Benign - melanocytic naevus
Malignant - melanoma
Treatment of melanoma?
Primary tumour - excised
Regional lymph node disease - lymph node excision or sentinel lymph node biopsy
Disseminated disease
- chemo
- immune therapy
- molecular targets
- palliative care
What does immune therapy in melanoma do?
Maintains T cell activation
What does Breslow’s depth measure?
The length of the tumour
Measure form the granular layer
Who is more prone to melanoma?
MM RISK Moles Moles - dysplastic type Red hair/freckles/blue eyes Inability to tan (burn easily) Sunburn Kindred (family history)
What macroscopic features are used to help diagnosis of melanoma?
Major features
-change in size, colour or shape
Minor features
- inflammation
- bleeding/crusting
- sensory change
- lesion diameter of 7mm or greater
What is the ABCDE for mole changes?
Asymmetry Borders Colour Diameter Evolution
List the hallmarks of cancer
Evade apoptosis Self-sufficiency in growth signals Insensitivity to anti-growth signals Tissue invasion and metastasis Sustained angiogenesis Limitless replicative potential
What normally happens in the MAPK pathway?
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
How do melanoma cells achieve self-sufficiency in growth signals?
Get NRas mutations
Braf mutations
These activate the MAPK pathway
How is melanoma with a BRAF mutation treated?
BRAF inhibitor
How do melanoma cells gain insensitivity to anti-growth signals?
Deletion of CDKN2A
This normally codes for two cyclin-dependent kinase inhibitors which normally cause for oncogene-induced senescence when oncogenes are activated
Why can a mutation to BRAF/NRas not necessarily cause cancer?
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
What are one of the two proteins that CDK2NA codes for? What is its function?
P14ARF - increases p53 activity
What does activation of the AKT pathway result in?
Evasion of apoptosis
What controls activation/suppression of the AKT pathway?
Activation
- activated by NRas and MAPK pathway
- PTEN encodes a protein which suppresses it (so loss of PTEN can activate it)
How do melanoma cells alter their adhesion to metastasise?
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
Why do chromosomes have telomeres?
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
What is replicative senescence?
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
Give an example of oncogene-induced senescence in melanoma
Cyclin-dependent kinase inhibitors such as p16 and p21 induce senescence if there is an NRas/BRAF mutation activating the MAPK pathway
How do cancer cells gain limitless replicative potential in melanoma?
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
How do breast cancers produce self-sufficient growth signals?
HER2 gene amplification
Where are melanocytes derived from?
Neural crest cells which migrate to many places
