Fig. 2

Mutations and mutational signatures in pre- and post-treatment tumors. a Mutations and mutational signatures in pre-treatment tumors. The top bar graph shows the number of mutations per trinucleotide sequence motif across all pre-treatment tumors. The bottom two bar graph shows the mutational signatures inferred in pre-treatment tumors. Two mutational signatures, matching previously described mutational signatures associated with APOBEC activity (cos sim = 0.99 with average of COSMIC Sig 2 and 13, = 0.82 with each individually), and nucleotide excision repair (NER) deficit (cos sim = 0.91 with COSMIC 5), were discovered. The NER signature also appears to have the aging signature embedded at a low level, which our data is unable to resolve. a Mutations and mutational signatures in post-treatment tumors. The top bar graph shows the number of mutations per trinucleotide sequence motif across all post-treatment tumors. The bottom bar graphs show the mutational signatures inferred in post-treatment tumors. Four mutational signatures were discovered, with three matching previously described signatures (APOBEC1: cos sim = 0.96 with COSMIC Sig 2; APOBEC2: cos sim = 0.95 with COSMIC Sig 13; NER: cos sim = 0.86 with COSMIC Sig 5) and an additional signature (UNK) not matching any previously described signature. b Mutations and mutational signatures from post-only mutations. Here we consider only those post-treatment mutations not found in matched pre-treatment tumors. The top bar graph shows the number of mutations per trinucleotide sequence motif, and the bottom graphs show mutational signatures inferred in these mutations. Three signatures were inferred, two of which matched previously discovered signatures (AGING: cos sim = 0.86 with COSMIC Sig 1; APOBEC: cos sim = 0.90 with average of COSMIC Sig 2 and 13; UNK: an additional unmatched signature). c Inferred mutational signature activity in pre-treatment tumors and post-treatment tumors. The majority of mutations are inferred to be due to mutational signatures associated with APOBEC activity and nucleotide excision repair (NER) deficit, but 14% of mutations in the post-treatment tumors are associated with an unknown mutational signature