Mutational Signatures (v3.2 - March 2021)
SBS90 · GRCh37 · COSMIC v94
Mutational profile using the conventional 96 mutation type classification. This classification is based on the six substitution subtypes: C>A, C>G, C>T, T>A, T>C, and T>G, as well as the nucleotides immediately 5’ and 3’ to the mutation.
Each of the substitutions is referred to by the pyrimidine of the mutated Watson—Crick base pair. Incorporating information on the bases immediately 5’ and 3’ to each mutated base generates 96 possible mutation types (6 types of substitution x 4 types of 5’ base x 4 types of 3’ base). Mutational signatures are displayed and reported based on the observed trinucleotide frequency of the genome, i.e., representing the relative proportions of mutations generated by each signature based on the actual trinucleotide frequencies of the corresponding reference genome.
Very strong sequence context enrichment, with a preference for thymines up to 4bp 3’ of mutated thymines.
Summary of the technical and experimental evidence available in the scientific literature regarding the validation of the mutational signature.
|Background||Identification study||First included in COSMIC|
|Boot et al. 2019 BioRxiv / Priestley et al. 2019 Nature||v3.1|
|Identification||NGS technique||Different variant callers||Multiple sequencing centres|
|Technical validation||Validated in orthogonal techniques||Replicated in additional studies||Extended context enrichment|
|Yes||Yes||Preference for T up to +4 bp|
|Proposed aetiology||Mutational process||Support|
|Duocarmycin exposure||Experimental confirmation|
|Experimental validation||Experimental study||Species|
|Boot et al. 2019 BioRxiv||Human|
Found in breast and oesophagus metastatic cancers treated with duocarmycin-based antibody-drug conjugates.
Transcriptional strand bias
SBS90 shows strong transcriptional strand bias for T>A substitutions with more mutated A than T bases on the untranscribed strands of genes compatible with damage to adenine.