SBS31 · 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

Prior chemotherapy treatment with platinum drugs.

Comments

SBS31 exhibits a pattern of mutations similar to components of SBS35 and both may be due to platinum drug treatment.

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
Boot et al. 2018 Genome Research 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
Platinum chemotherapy Experimental confirmation
Experimental validation Experimental study Species
Boot et al. 2018 Genome Research Human

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

SBS31 is associated with DBS5, which is predominantly characterized with CT>AA mutations.

Transcriptional strand bias

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Transcriptional strand bias of C>T mutations with more G than C mutations on the untranscribed strands of genes consistent with damage to guanine and repair by transcription-coupled nucleotide excision repair.