Figure 2: The spectrum of mutations in human samples is dominated by C toT transitions and show increasing mutation burden across cuSCC development. | Nature Communications

Figure 2: The spectrum of mutations in human samples is dominated by C toT transitions and show increasing mutation burden across cuSCC development.

From: Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

Figure 2

(a) cuSCC display very high mutational loads of 45.7 variants per Mb, with NS and AK samples harbouring an average of 5.8 and 18.5 variants per Mb, respectively. There are strongly dominated by single nucleotide variants. (b) NMF-derived orthogonal mutational profiles derived from over 6,000 human cancers confirm a strong enrichment for CpG-associated C→T transitions classically associated with UVB exposure, particularly for AK and cuSCC. For each lesion, the proportion of mutations attributable to a specific signature is plotted as a function of total mutation counts. This correlates strongly with the increasing mutational burden observed in AK and cuSCC, suggesting that the increase is attributable solely to UVB exposure. Three other profiles dominated by C→T transitions are significantly represented in the mutational data and relatively enriched in NS, including ones first described in the context of temozolamide exposure (Tem), one attributed to liver toxins, and one associated with CpG sites. These latter two signatures likely reflect background mutational processes in this context. (c) SMG from this cohort, match those identified previously studied cohorts of cuSCC.

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