Mutational Signatures (v3.2 - March 2021)
SBS21 · GRCh37 · COSMIC v95
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.
DNA mismatch repair deficiency.
SBS21 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, SBS20, SBS26, and SBS44.
|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|
|Proposed aetiology||Mutational process||Support|
|MMR deficiency||Statistical association; Experimental studies|
|Experimental validation||Experimental study||Species|
|Meier et al. 2018 Genome Research||C. elegans|
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.
Transcriptional strand bias
Transcriptional strand bias with more mutated T than A on untranscribed strands of genes compatible with damage to thymidine and activity of transcription-coupled nucleotide excision repair.
Differences between current and previous profiles
Reduced contamination by other signatures of DNA mismatch repair deficiency. The cosine similarity between the prior and current versions of SBS21 is 0.95