SBS7b · GRCh37 · COSMIC v95

Mutational profile

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Genome: GRCh37

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

SBS7a/SBS7b/SBS7c/SBS7d are found in cancers of the skin from sun exposed areas and are likely to be due to exposure to ultraviolet light. SBS7b may possibly be the consequence of just one of the two major known UV photoproducts, cyclobutane pyrimidine dimers or 6-4 photoproducts. However, there is no evidence for this hypothesis and it is unclear which of these photoproducts may be responsible for SBS7b.

Acceptance criteria

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
Hayward et al. 2017 Nature v3
Identification NGS technique Different variant callers Multiple sequencing centres
WES & WGS Yes Yes
Technical validation Validated in orthogonal techniques Replicated in additional studies Extended context enrichment
Yes Yes -
Proposed aetiology Mutational process Support
UV light 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

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Numbers of mutations per megabase attributed to the mutational signature across the cancer types in which the signature was found. Each dot represents an individual sample and only samples where the signature is found are shown. The number of mutations per megabase was calculated by assuming that an average whole-exome has 30 Mb with sufficient coverage, whereas an average whole-genome has 2,800 Mb with sufficient coverage.

The numbers below the dots for each cancer type indicate the number of high confidence tumours in which at least 10 mutations were attributed to the signature (above the blue horizontal line) and the total number of high confidence tumours analysed (below the blue horizontal line). Only high confidence data are displayed: samples with reconstruction accuracy >0.90. The number of mutations per megabase was calculated by assuming that an average exome has 30 Mb with sufficient coverage, whereas an average whole genome has 2,800 Mb with sufficient coverage.

Associated signatures

SBS7b is associated with SBS7a/SBS7c/SBS7d and these signatures are commonly found in the same samples. SBS7b is associated with DBS1, which exhibits predominantly CC>TT mutations and also with ID13, which is predominantly characterised by T deletions at TT dinucleotides.

Transcriptional strand bias

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Transcriptional strand bias with more mutated C than G bases on untranscribed strands of genes compatible with damage to cytosine and activity of transcription-coupled nucleotide excision repair.

Differences between current and previous profiles

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Genome: GRCh37

The much larger number of melanoma whole genome sequences now analysed allows splitting of SBS7 into four distinct components. These are termed SBS7a/SBS7b/SBS7c/SBS7d that together recapitulate the prior pattern of SBS7 (0.95 similarity between SBS7a & SBS7 v2 / 0.88 similarity between SBS7b & SBS7 v2 / 0.10 similarity between SBS7c / SBS7 v2 and 0.10 similarity between SBS7d & SBS7 v2).