SBS10c · GRCh37 · COSMIC v93

Mutational profile

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.

v3.2_SBS10c_PROFILE_GA_GRCh37.jpg

Genome: GRCh37

Proposed aetiology

Defective POLD1 proofreading.

Comments

Strong lagging replication strand bias. Enriched in non-coding genome (intergenic and intronic) regions.

Acceptance criteria

Summary of the technical and experimental evidence available in the scientific literature regarding the validation of the mutational signature.

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
Robinson et al. 2021 BioRxiv v3.2
Identification NGS technique Different variant callers Multiple sequencing centres
WGS No No
Technical validation Validated in orthogonal techniques Replicated in additional studies Extended context enrichment
Yes No -
Proposed aetiology Mutational process Support
Defective POLD1 proofreading Statistical association
Experimental validation Experimental study Species
- -

Tissue distribution

Normal tissues from individuals with germline POLD1 exonuclease domain mutations

Associated signatures

Associated with ID1.

Differences between current and previous profiles

v3.2_SBS10c_DIFFERENCE_GA_GRCh37.jpg

Genome: GRCh37