Extended Data Figure 2: SMGs and the role of APOBEC in cervical cancer mutagenesis.

a–f, High-confidence somatic mutations in SMGs among 192 exome-sequenced samples in the extended case set are shown. Domains are labelled according to Gencode 19, corresponding to Ensembl 74. Mutations at canonical intronic splice acceptor (e−1 and e−2) are labelled based on proximity to the nearest coding exon. Panels display somatic mutations detected in novel cervical cancer SMGs, with HLA-B included for comparison with its family member HLA-A. Each axis is the protein-coding portion of a gene and each highlighted section represents the UniProt functional domain. Vertical lines indicate the boundaries of multiple annotation sources within common domain annotations as outlined in Supplementary Table 5. Horizontal lines distinguish overlapping domains. Circles represent a single mutation and are coloured based on mutation type. Mutations present in squamous cell carcinomas are black, whereas those present in adenocarcinomas are pink. g, PIK3CA mutations and recurrence are shown in a stacked circle plot, as above. Additionally, lolliplot sticks are coloured red if the mutation type coincides with patterns of APOBEC mutagenesis. h, The minimal estimated number of APOBEC-induced mutations (APOBEC_MutLoad_MinEstimate column in Supplementary Table 1) strongly correlates with total number of mutations in a sample, as well as with the number of single-nucleotide variants (SNVs) in G:C pairs that are the exclusive substrate for mutagenesis by APOBEC cytidine deaminases. Although correlation with mutagenesis in A:T base pairs, which cannot be mutated by APOBEC enzymes, is statistically significant (two-tailed P = 0.047), it is very weak. Pearson correlation and R² were calculated for all 192 exome-sequenced samples, including samples with zero values. Only samples with non-zero values of APOBEC_MutLoad_MinEstimate are presented.