Signature 1 is the result of an endogenous mutational process initiated by spontaneous deamination of 5-methylcytosine.
Signature 2 has been attributed to activity of the AID/APOBEC family of cytidine deaminases. On the basis of similarities in the sequence context of cytosine mutations caused by APOBEC enzymes in experimental systems, a role for APOBEC1, APOBEC3A and/or APOBEC3B in human cancer appears more likely than for other members of the family.
Signature 3 is associated with failure of DNA double-strand break-repair by homologous recombination.
Signature 4 is associated with smoking and its profile is similar to the mutational pattern observed in experimental systems exposed to tobacco carcinogens (e.g., benzo[a]pyrene). Signature 4 is likely due to tobacco mutagens.
The aetiology of Signature 5 is unknown.
Signature 6 is associated with defective DNA mismatch repair and is found in microsatellite unstable tumours.
Based on its prevalence in ultraviolet exposed areas and the similarity of the mutational pattern to that observed in experimental systems exposed to ultraviolet light Signature 7 is likely due to ultraviolet light exposure.
The aetiology of Signature 8 remains unknown.
Signature 9 is characterized by a pattern of mutations that has been attributed to polymerase η, which is implicated with the activity of AID during somatic hypermutation.
It has been proposed that the mutational process underlying this signature is altered activity of the error-prone polymerase POLE. The presence of large numbers of Signature 10 mutations is associated with recurrent POLE somatic mutations, viz., Pro286Arg and Val411Leu.
Signature 11 exhibits a mutational pattern resembling that of alkylating agents. Patient histories have revealed an association between treatments with the alkylating agent temozolomide and Signature 11 mutations.
The aetiology of Signature 12 remains unknown.
Signature 13 has been attributed to activity of the AID/APOBEC family of cytidine deaminases converting cytosine to uracil. On the basis of similarities in the sequence context of cytosine mutations caused by APOBEC enzymes in experimental systems, a role for APOBEC1, APOBEC3A and/or APOBEC3B  in human cancer appears more likely than for other members of the family. Signature 13 causes predominantly C>G mutations. This may be due to generation of abasic sites after removal of uracil by base excision repair and replication over these abasic sites by REV1.
The aetiology of Signature 14 remains unknown.
Signature 15 is associated with defective DNA mismatch repair.
The aetiology of Signature 16 remains unknown.
The aetiology of Signature 17 remains unknown.
The aetiology of Signature 18 remains unknown.
The aetiology of Signature 19 remains unknown.
Signature 20 is believed to be associated with defective DNA mismatch repair.
The aetiology of Signature 21 remains unknown.
Signature 22 has been found in cancer samples with known exposures to aristolochic acid. Additionally, the pattern of mutations exhibited by the signature is consistent with the one previous observed in experimental systems exposed to aristolochic acid.
The aetiology of Signature 23 remains unknown.
Signature 24 has been found in cancer samples with known exposures to aflatoxin. Additionally, the pattern of mutations exhibited by the signature is consistent with that previous observed in experimental systems exposed to aflatoxin.
The aetiology of Signature 25 remains unknown.
Signature 26 is believed to be associated with defective DNA mismatch repair.
The aetiology of Signature 27 remains unknown.
The aetiology of Signature 28 remains unknown.
Signature 29 has been found in cancer samples from individuals with a tobacco chewing habit.
The aetiology of Signature 30 remains unknown.