We report on a systematic analysis of genotype-specific melanocyte (MC) UVR responses in transgenic mouse melanoma models along with tumour... » More

We report on a systematic analysis of genotype-specific melanocyte (MC) UVR responses in transgenic mouse

melanoma models along with tumour penetrance and comparative histopathology. pRb or p53 pathway

mutations cooperated with NrasQ61K to transform MCs. We previously reported that MCs migrate from the

follicular outer root sheath into the epidermis after neonatal UVR. Here, we found that Arf or p53 loss markedly

diminished this response. Despite this, mice carrying these mutations developed melanoma with very early age

of onset after neonatal UVR. Cdk4R24C did not affect the MC migration. Instead, independent of UVR exposure,

interfollicular dermal MCs were more prevalent in Cdk4R24C mice. Subsequently, in adulthood, these mutants

developed dermal MC proliferations reminiscent of superficial congenital naevi. Two types of melanoma were

observed in this model. The location and growth pattern of the first was consistent with derivation from the

naevi, while the second appeared to be of deep dermal origin. In animals carrying the Arf or p53 defects, no

naevi were detected, with all tumours ostensibly skipping the benign precursor stage in progression.

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