SBS20 · GRCh37 · COSMIC v95

Mutational profile

v3.2_SBS20_PROFILE_GA_GRCh37.jpg

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

Concurrent POLD1 mutations and defective DNA mismatch repair.

Comments

SBS20 is one of seven mutational signatures associated with defective DNA mismatch repair and microsatellite instability (MSI) and is often found in the same samples as other MSI associated signatures: SBS6, SBS14, SBS15, SBS21, SBS26, and SBS44.

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
Alexandrov et al. 2013 Nature v1
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
MMR deficiency + POLD1 mutation Statistical association; Experimental studies
Experimental validation Experimental study Species
Meier et al. 2018 Genome Research C. elegans

Tissue distribution

v3.2_SBS20_TISSUE.jpg

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

SBS20 is associated ID1 and ID2.

Transcriptional strand bias

v3.2_SBS20_STRAND_BIAS.jpg

Differences between current and previous profiles

v3.2_SBS20_DIFFERENCE_GA_GRCh37.jpg

Genome: GRCh37

Reduced contamination by other DNA mismatch deficiency signatures. The cosine similarity between the prior and current versions of SBS20 is 0.78.