Mutagen | Dominant mutations* | Extended context* | Studies reporting mutation signatures | Prevalence | Challenges |
---|---|---|---|---|---|
Exogenous | Â | Â | Â | Â | Â |
Aristolochic acid | A > T | (C|T)AG > (C|T)TG | 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 | 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 | 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 | Signature in extended context not known | ||
Temozolomide | C > T | CC > TC; CT > TT | Present in 10% of glioblastomas; 9% of melanoma [8] | No unusual challenges | |
Benzene | C > T; C > A | NA | [38] | Several mutagenic metabolites and signature in extended context not known | |
Endogenous | Â | Â | Â | Â | Â |
Activated APOBEC | C>T | TCA>TTA | 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 | 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 |