Exome analysis of UVA and UVB accelerated melanomas (mouse)

Exome sequencing was performed on melanomas from two genetically engineered mouse models: TN and TB. TN mice are homozygous for the LSL-NrasQ61R allele. TB animals carry a heterozygous, conditional BrafV637E allele. Both models harbor a conditional p16INK4a knockout allele and melanocyte-specific Cre transgene (Tyr::CreER(T2)). On post natal days 1 and 2 the mice were treated with 4-hydroxytamoxifen to induce melanocyte-specific oncogene expression and p16INK4a loss. The animals were then subjected to a single dose of either mock (No UV), UVA (70 kJ/m2) or UVB irradiation (4.5 kJ/m2). Mice were monitored for spontaneous tumor formation. Resulting melanomas were harvested at euthanasia and whole exome sequencing performed to detect UVA- and UVB-dependent mutational patterns.