Mutational Signatures (v3.5 - November 2025)
SBS22a · GRCh37 · COSMIC v103
Mutational profile
Genome: GRCh37
Genome: GRCh38
Genome: mm9
Genome: mm10
Genome: rn6
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.
Proposed aetiology
Aristolochic acid exposure. Found in cancer samples with known exposures to aristolochic acid and the pattern of mutations exhibited by the signature is consistent with that observed in experimental systems of aristolochic acid exposure.
Acceptance criteria
| Background | Identification study | First included in COSMIC | |
|---|---|---|---|
| Senkin et al. 2023 MedRxiv | v3.4 | ||
| Identification | NGS technique | Different variant callers | Multiple sequencing centres |
| WGS/WES | Yes | Yes | |
| Technical validation | Validated in orthogonal techniques | Replicated in additional studies | Extended context enrichment |
| Yes | Yes | - | |
| Proposed aetiology | Mutational process | Support | |
| Aristolochic acid exposure | Experimental confirmation | ||
| Experimental validation | Experimental study | Species | |
| Nik-Zainal et al. 2015 Mutagenesis | Mouse | ||
Summary of the technical and experimental evidence available in the scientific literature regarding the validation of the mutational signature.
Tissue distribution
Found in liver, kidney, biliary tract, oesophageal squamous, and bladder cancers.
Associated signatures
SBS22a is associated with SBS22b, and these signatures are commonly found in the same samples, although individuals with only SBS22a have been identified. SBS22a is also associated with DBS20 and ID23.
Differences between current and previous profiles
Genome: GRCh37
Genome: GRCh38
Genome: mm9
Genome: mm10
Genome: rn6
SBS22a is the equivalent of the signature previously known as SBS22. The cosine similarity between SBS22 and SBS22a is 0.995.