Fig. 4

Unusually elevated proportions of apolipoprotein B mRNA-editing enzyme catalytic polypeptide–like (APOBEC) and clock-like mutagenesis in a nasal septal squamous cell carcinoma (SCC). The y-axis represents the percentage of mutations in a given cancer attributable to COSMIC signature 2 (APOBEC), signatures 2 and 13 (APOBEC subset), signature 5 (clock-like), and signature 4 (tobacco), which are shown on the x-axis. The dots represent 279 The Cancer Genome Atlas (TCGA) head-and-neck SCCs (yellow, except for 27 tumors in the 90th percentile for signature 2 proportion, represented in brown), 38 cutaneous SCCs (blue), and our nasal septal SCC (red). Our patient’s nasal septal SCC is in the 90th percentile for both COSMIC signatures 2 and 5 independently, and in the 80th percentile for signatures 2 and 13. The SCCs in the 90th percentile for signature 2 (brown, first column) show good concordance with elevated COSMIC signature 2 and 13 proportions (overall APOBEC, second column), but not with COSMIC signature 5 (clock-like , third column). Therefore, the fact that our tumor scores highly in both APOBEC and clock-like signatures is unusual, and more closely resembles the tissue damage SCCs reported in recessive dystrophic epidermolysis bullosa [1].