Fig. 5: Mutation profiles of XP-V skin cancers and POLH-KO clones.
From: Genomic mutation landscape of skin cancers from DNA repair-deficient xeroderma pigmentosum patients
a Trinucleotide-context mutation profile of genomic SBS (upper panel) and genic SBS (lower panel) separated by transcribed (TR) and untranscribed (NT) strands in XP-V tumors. Blue bars— untranscribed strand for purines or transcribed for pyrimidines, red bars—transcribed strand for purines or untranscribed for pyrimidines. Data are presented as mean values +/− SEM. n = 14 tumors. b Fractions of C > A mutations separated by gene strands in the TSS-centered 100 kb region of XP-V tumors (binned by 10 kb intervals). Blue—untranscribed strand for mutations from purines and transcribed strand for mutations from pyrimidines; red— transcribed strand for mutations from purines and untranscribed strand for mutations from pyrimidines. Data are presented as mean values +/− SEM. n = 14 tumors. c The transcriptional bias (ratio between transcribed and untranscribed strand) for C > A and C > T mutations per bin of gene expression level (only XP-V samples represented by BCC, n = 11 tumors). Data are presented as mean values +/− SEM. d Trinucleotide-context mutation profiles of SBS separated by strands in XP-V tumors for C > A and T > A mutations. Data are presented as mean values +/− SEM, n = 14 tumors. e Mutations per megabase in the POLH wt and POLH-KO clones in nontreated cells (NT, n = 1 per cell line independent biological replicate), treated with KbrO3 (n = 1 per cell line independent biological replicate), UV-A (n = 3 per cell line independent biological replicates) and UV-C (n = 3 independent cell clones per cell line). Welch two sample t-test, two-sided. Data are presented as mean values +/− SEM. Source data are provided as a Source Data file. f Mutational specificity of the TG > TT mutations in XP-V tumors and POLH-KO UV-A- and UV-C-treated cell lines. X-axis: log2-transformed transcriptional bias of the TG > TT mutations per genome. Y-axis: Fraction of the mutations in the TG > TT context from the total number of C:G > A:T substitutions per genome. POLH-KO and POLH-wt clones are specifically indicated with their corresponding treatment (KbrO3, UV-A and UV-C) as well as COSMIC SBS18 and SBS36 mutational signatures associated with oxidative DNA damage (black dots). g Mutation profiles of the POLH-wt and POLH-KO clones for nontreated cells (NT), treated with KbrO3, UV-A and UV-C. Data are presented as mean values +/− SEM for UV-A and UV-C experiments. Sample size is indicated on the plots (independent cell clones).
