SBS92 · GRCh37 · COSMIC v93

Mutational profile

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.

v3.2_SBS92_PROFILE_GA_GRCh37.jpg

Genome: GRCh37

Proposed aetiology

Associated with tobacco smoking.

Comments

SBS92 activity was found increased in bladder tumours, as well as in normal urothelium of tobacco ever smokers compared to never smokers.

Acceptance criteria

Summary of the technical and experimental evidence available in the scientific literature regarding the validation of the mutational signature.

Supporting evidence for mutational signature validity

Validated evidence for real signature
Unclear evidence for real signature
Evidence for artefact signature
Background Identification study First included in COSMIC
Lawson et al. 2020 Science v3.2
Identification NGS technique Different variant callers Multiple sequencing centres
WGS Yes Yes
Technical validation Validated in orthogonal techniques Replicated in additional studies Extended context enrichment
Yes Yes -
Proposed aetiology Mutational process Support
Tobacco smoking Statistical association
Experimental validation Experimental study Species
- -

Tissue distribution

Predominately found in bladder normal and neoplastic tissue.

Associated signatures

SBS4, ID3 and DBS2 have also been found associated with tobacco smoking.

Transcriptional strand bias

SBS92 exhibits strong transcriptional strand bias consistent with damage on purines for all types of single base substitutions.

v3.2_SBS92_STRAND_BIAS.jpg