Extended Data Fig. 7: Cross-contamination of cancer mutation enrichments at AAWWTT sequences.

a, A heat map of SBS pentanucleotide change patterns in colorectal cancer (CRC) genomes based on the PCAWG project, n=60. The results indicate that the established hypermutator-associated SBS signature SBS28 strongly affects one AAWWTT-associated pentanucleotide sequence (red arrow). SBS28 possibly biases AAWWTT mutation estimates (leftmost annotation column for AAWWTT-derived pentanucleotide signature) in POLE/POLD1-mutated CRCs. b, A heat map of SBS pentanucleotide change patterns in stomach adenocarcinoma (STAD) genomes based on the PCAWG project, n=75. The results indicate that the established SBS signature SBS17b strongly affects two AAWWTT-associated pentanucleotide sequences (red arrows). SBS17b possibly biases AAWWTT mutation estimates (leftmost annotation column for AAWWTT-derived pentanucleotide signature) in STADs. The heatmaps show relative proportions of pentanucleotide changes (n=133, rows) associated with AAWWTT-related sequences or SBS28/SBS17b trinucleotide changes. The rows are ordered by the strength of expected contribution from SBS28 (CRC, A) or SBS17b (STAD, B) signatures, followed by AAWWTT contributions. Expected contributions from each signature to pentanucleotide changes are shown as color code on the top of the heatmap for each row. The left part of the heatmap represents pentanucleotide changes with contributions greater than zero in SBS28 or SBS17b (A or B, respectively), whereas the right part represents pentanucleotide changes with expected contributions of zero. Estimated contributions of SBS28, SBS17b and SBSA per tumor sample that are greater than zero are shown as a color code on the left of the heatmap. Black marks on the left mark cases with protein-coding gene-changing mutations in POLE or POLD1. The weighted sum of AAWWTT-related mutation proportions are shown as a color code in the leftmost annotation column. Red arrows below the heatmap denote AWWTT-associated pentanucleotide changes with high contributions from SBS28 or SBS17b.