Skip to main content

Table 1 Examples of exogenous mutagens and endogenous mutagenic processes

From: Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention

Mutagen

Dominant mutations*

Extended context*

Studies reporting mutation signatures

Prevalence

Challenges

Exogenous

     

Aristolochic acid

A > T

(C|T)AG > (C|T)TG

[16–19]

Widely used in traditional medicines [20]; exposure to AA is widespread in Taiwan [17]

No unusual challenges

UV radiation

C > T;

strand bias; CC > TT

TC > TT (C|T)C > (C|T)T

[6, 8, 9, 21–23]

Prevalence of signature: 87% of melanoma [8]

No unusual challenges

Tobacco smoke

Primarily C > A, some C > G and C > T

CG > AG

CG > TG;

CG > GG

[8, 14, 24–26]

Extensive epidemiological evidence of the role of tobacco smoke in cancer [27, 28]

Contains multiple carcinogens with individually unknown signatures

Aflatoxin B1

Primary G > T;some G > A

NA

[29–34]

[29, 35]

Signature in extended context not known

Temozolomide

C > T

CC > TC; CT > TT

[8, 36, 37]

Present in 10% of glioblastomas; 9% of melanoma [8]

No unusual challenges

Benzene

C > T;

C > A

NA

[38]

Exposure associated with risk of leukemia [39, 40]

Several mutagenic metabolites and signature in extended context not known

Endogenous

     

Activated APOBEC

C>T

TCA>TTA

[8, 41, 42]

Present in 16 tumor types [8]

Signatures 2 and 13 are similar [8], except 2 has C > T and 13 has higher C > G

Mutated DNA polymerase epsilon

C > T

TCG > TTG; TCT > TAT

[8, 13]

Present in 13.7% of uterus cancer and 36.7% of colorectal cancer [8]

No unusual challenges

Mismatch repair deficiency (MSI)

C > T;

C > A

CG > TG; CT > AT;

homopolymer and microsatellite length changes

[8]

Present in 9 tumor types [8]

No unusual challenges

Correlated with patient age

C > T

CG > TG

[8]

A majority of tumors of most types have this signature [8]

Interpretation of two similar signatures in [8] not clear

  1. *The ' > ' symbol indicates a change from one nucleotide to another; a vertical line indicates alternative nucleotides. NA, not applicable.