Table 1.

Summary of relationships between each mutational signature and various genomic features. The 20 mutational signatures are noted in the left-most column. This is followed by information on mutation classes, features that predominantly characterize each signature, and associated etiologies, if known. Relationships relating to transcriptional strands, replication time, and strands and chromatin organization are also noted.

Mutational signatureMutation typePredominant features of signatureAssociated mutational processTranscriptional strandReplicative strandReplication timeChromatin organization
1SubC>T at CpGDeamination of methyl-cytosine (age associated)Some biasEnriched late
5SubT>CUncertain (age associated)Some biasSome biasEnriched lateSlight enrichment at linker
2SubC>T at TpCpNAPOBEC relatedSome biasStrong lagging strand biasEnriched late
13SubC>G at TpCpNAPOBEC relatedSome biasStrong lagging strand biasFlat
6SubC>T (and C>A and T>C)MMR deficientSome biasFlat
20SubC>A (and C>T and T>C)MMR deficientSome biasEnriched late
26SubT>CMMR deficientSome biasStrong biasEnriched lateEnriched at linker
3SubHR deficientSome biasSome biasEnriched late
8SubC>AAmplified by HR deficiency?Some biasEnriched late
18SubC>AUncertainSome biasSome biasEnriched lateEnriched at nucleosomes and periodic
17SubT>GUncertainSome biasEnriched lateEnriched at nucleosomes and periodic
30SubC>TUncertainFlat
RS1RearrLarge tandem duplications (>100 kb)Uncertain type of HR deficiency?NANAEnriched early
RS2RearrDispersed translocationsNANAEnriched early
RS3RearrSmall tandem duplications (<10 kb)HR deficiency (BRCA1)NANAEnriched early
RS4RearrClustered translocationsNANAEnriched early
RS5RearrDeletionsHR deficientNANAEnriched early
RS6RearrOther clustered rearrangementsNANAEnriched early
Repeat-medIndel<3 bp indel at polynuc tractMMR deficientNANAEnriched lateEnriched at linker and periodic
MicrohomIndel≥3 bp indel with MMEJ-junctionsHR deficientNANAEnriched late

Abbreviations: MMEJ, microhomology-mediated end joining; NA, not available; polynuc, polynucleotide; Rearr, rearrangement; Sub, substitution.

Reprinted by permission from Macmillan Publishers Ltd.: Nature Communications 7:11383, copyright 2016.