Genomic profiling of treatment-naïve tumor revealed high TMB at baseline that may have been the result of UV exposure, producing the driver mutations in TP53 and CDKN2A. TMB analysis of his autopsy tumor samples demonstrated an increase of ∼20–37 additional mut/Mb that could be attributed to the truncal amplification of the A3 subfamily of cytidine deaminases, as indicated by the presence of APOBEC-specific Signature 2, and/or potentially therapy-induced mutations. The gene discussed is CDA; the disease is neoplasm.