To study the mutagenic mechanisms by which acute sunburn accelerates MM, we sequenced the exomes of spontaneous and neonatal UVB-induced Cdk4-R24C::Tyr-NRASQ61K mouse MMs.
Here, using a bigenic mouse model system combining mutant oncogenic NRAS(Q61K) (constitutively active RAS) or mutant activated CDK4(R24C/R24C) (prevents binding of CDK4 by kinase inhibitor p16(INK4A)) with an epidermis-specific knockout of the nuclear retinoid X receptor alpha (RXRα(ep-/-)) results in increased melanoma formation after chronic ultraviolet-B (UVB) irradiation compared with control mice with functional RXRα.
We previously showed that mice carrying an activated Cdk4 mutation together with melanocyte-specific mutant Hras (Cdk4(R24C/R24C)/TPras) develop melanoma spontaneously, but penetrance is increased and age of onset reduced after neonatal ultraviolet radiation (UVR) exposure.