Melanoma Flashcards
What type of cells become cancerous in melanoma?
Melanocytes
What are some risk factors of melanoma?
UV exposure, moles, skin colour and freckling, sunbeds, family history, previous cancers, lowered immunity
What are the clinical features of melanoma?
Dark mole, inflamed moles, mole with irregular borders
What does UV stimulate the production of?
Melanocortin, the ligand for MC1R
What does normal and mutated MC1R result in the production of?
Eumelanin (sun-protective pigment); pheomelanin
What growth factors are produced by UV, and what cells are they produced in?
FGF and TGT, on melanocytes and surrounding keratinocytes
What effect can mutated DNA have on oncogenes and tumour-suppressor genes?
Activation of oncogenes and loss of tumour-suppressor genes
What oncogenes are activated in melanoma?
BRAF, NRAS
What tumour suppressor genes are lost in melanoma?
CDKN2A
What is the most common genetic mutation in melanoma?
BRAF
Where are FGF and TGF transduced, and what does this trigger?
Via the Ras/RAF pathway. Triggers the transcription of genes involved in cellular proliferation and migration
What gene (and its products) is frequently targeted for disruption in melanoma?
CDKN2A and its products p16 and p14ARF
What happens when p16 is defective?
It’s unable to inactivate CDK4 and CDK6 (which phosphorylate Rb), releasing the transcription factor E2F and leading to cell cycle progression
What is the result of mutations in p14ARF?
Allows degradation of p53 by releasing its binding partner
What is a further defence of melanoma cells?
Express high levels of anti-apoptic molecules Bcl-2 and Bcl-x
