ID18 · GRCh37 · COSMIC v94

Mutational profile

The height of each mutational profile bar represents the proportion of one ID mutation type among all ID mutation types in the signature. Although there is no single intuitive and naturally constrained set of ID mutation types (as there arguably are for SBSs and DBSs), an 83 subclass categorisation of ID mutations was designed.

The 83 ID classification incorporates the prior knowledge that IDs commonly have sizes of 1-10 bps, that both insertions and deletions exist, that IDs of C and T occur at different rates, that IDs preferentially occur at repetitive elements, that the length of the repeat unit may influence the likelihood of an ID occurring, that the number of repeat units in a repeat stretch may influence the likelihood of an ID occurring, that IDs are also fostered in some instances by overlapping sequence microhomologies at the ID boundaries and that different mutational processes may, in principle, be differently influenced by these features. We therefore designed an 83 subclass categorisation of IDs that allows some exploration of all the above possibilities, while constraining the number of categories in order to accommodate the relatively small numbers of IDs (compared to substitutions) found in most genomes. This classification categorises IDs of lengths from 1bp to >5bp, for 1bp IDs classifies them as T or C and the number of single base repeats they occur in from 0 to >5, categorises lengths of non-single base repeat units from 2bp to >5bp and the number of repeats from 1 to >5 and size of microhomology from 0bp to >5bp. We recognise that different classifications of IDs may be preferred by others. The ID mutation types are enumerated in the following Excel document.

v3.2_ID18_PROFILE_GA_GRCh37.jpg

Genome: GRCh37

Proposed aetiology

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

Comments

Strong preference for adenines 5' of homopolymer containing the deletion.

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
Lee-Six et al. 2019 Nature / Pleguezuelos-Manzano et al. 2020 Nature / Boot et al. 2019 BioRxiv v3.1
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 Preference for A 5' of homopolymer
Proposed aetiology Mutational process Support
Colibactin exposure Experimental confirmation
Experimental validation Experimental study Species
Pleguezuelos-Manzano et al. 2020 Nature Human

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 SBS88, also arising from colibactin exposure.