Table 3. Mutational signatures of wild-type and mismatch repair defective cells with and without exposure to alkylating agents.
Mutation | Species | Reporter sequence | Tissue | Inducing agent | Percent C:G>T:A (%) | Percent C:G>T:A at CpG (%) | Percent C:G>T:A at CpC (%) | Percent T:A>C:G (%) | Percent C:G>A:T (%) | Percent ins/del (%) | Reference |
---|---|---|---|---|---|---|---|---|---|---|---|
Msh6−/− | Mouse | lacI | Small intestine | Spontaneous | 73 | 58 | — | 11 | 5 | 9 | (15) |
Wild type | Mouse | lacI | Small intestine, thymus | Spontaneous | 50 | 80 | 0 | 13 | — | 9 | (16) |
Wild type | Mouse | lacI | Small intestine, thymus | N -methyl-Nnitrosourea | 74 | 7 | 59 | 0 | — | 8 | (16) |
Msh2−/− | Mouse | lacI | Small intestine, thymus | Spontaneous | 42 | 60 | 20 | 25 | — | 17 | (16) |
Msh2−/− | Mouse | lacI | Small intestine, thymus | N-methyl-Nnitrosourea | 82 | 15 | 65 | 0 | — | 16 | (16) |
hMSH6 3510del5 868delC | Human | HPRT | HCT15 colorectal cancer cell line | Spontaneous | 25 | 41 | 19 | 6 | 46 | 5 | (17) |
hMSH6 D1145V V1192I | Human | HPRT | MT1 cells | Spontaneous | 0 | 0 | 0 | 60 | 20 | 20 | (18) |
hMSH6 D1145V V1192I | Human | HPRT | MT1 cells | N′-Methyl-N ’-nitro-N -nitrosoguanidine | 94 | 0 | 43 | 0 | 1 | 0 | (18) |
hMSH6 Het C1453T, Q485X; Het G3907A, A1303T | Human | 500 kb (exons of protein kinases) | PD1487a | Temozolomide | 100 | 0 | 47 | 0 | 0 | 0 | This study |
hMSH6 Hom delG2425, V809X | Human | 500 kb (exons of protein kinases) | PD1489a | Temozolomide and BCNU | 97 | 7 | 55 | 0 | 3 | 0 | This study |
NOTE: The 5′ (underlined) cytosine in the CpC dinucleotide is the one mutated.
Abbreviations: HPRT, hypoxanthine phosphoribosyltransferase; BCNU, 1,3-bis(2-chloroethyl)-1-nitrosourea.