Mutational Signatures (v3.2 - March 2021)
SBS30 · GRCh37 · COSMIC v94
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.
SBS30 is due to deficiency in base excision repair due to inactivating mutations in NTHL1.
Summary of the technical and experimental evidence available in the scientific literature regarding the validation of the mutational signature.
|Background||Identification study||First included in COSMIC|
|Alexandrov et al. 2015 Nature Genetics / Nik-Zainal et al. 2016 Nature||v2|
|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|
|BER deficiency||Experimental confirmation|
|Experimental validation||Experimental study||Species|
|Drost et al. 2017 Science||Human|
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
Differences between current and previous profiles
The cosine similarity between the prior and current versions of signature SBS30 is 0.96.