SBS88 · · COSMIC v91

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 (all substitutions are referred to by the pyrimidine of the mutated Watson—Crick base pair). Show more

Further, each of the substitutions is examined by incorporating information on the bases immediately 5’ and 3’ to each mutated base generating 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 human genome, i.e., representing the relative proportions of mutations generated by each signature based on the actual trinucleotide frequencies of the reference human genome version GRCh37.


Proposed aetiology

Exposure to E.coli bacteria carrying pks pathogenicity island, producing genotoxic compound colibactin.

Comments

SBS88 appears to be most active in the first decade of life. Strong preference for adenines at positions -3 and -4 (i.e. 5' of the mutation).


Tissue distribution

Mainly found in colorectal cancers and normal colorectal epithelial cells, as well as in some samples derived from head and neck cancer, urinary tract cancer and oral squamous cell carcinoma.


Associated signatures

Associated with ID18, also arising from colibactin exposure.


Transcriptional strand bias

SBS88 exhibits transcriptional strand bias, with more mutations occurring when the T base is on the transcribed rather than on the untranscribed DNA strand. Interestingly, genotoxic compound colibactin is known to form adenine adducts (as well as double-strand breaks), a type of DNA damage which is often repaired by the transcription-coupled nucleotide excision repair system, which is principally responsible for transcriptional strand bias.

tbs patterns