Table 3.

Mutational signatures of wild-type and mismatch repair defective cells with and without exposure to alkylating agents

MutationSpeciesReporter sequenceTissueInducing agentPercent 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−/−MouselacISmall intestineSpontaneous73581159( 15)
Wild typeMouselacISmall intestine, thymusSpontaneous50800139( 16)
Wild typeMouselacISmall intestine, thymusN-methyl-N-nitrosourea7475908( 16)
Msh2−/−MouselacISmall intestine, thymusSpontaneous4260202517( 16)
Msh2−/−MouselacISmall intestine, thymusN-methyl-N-nitrosourea821565016( 16)
hMSH6 3510del5 868delCHumanHPRTHCT15 colorectal cancer cell lineSpontaneous2541196465( 17)
hMSH6 D1145V V1192IHumanHPRTMT1 cellsSpontaneous000602020( 18)
hMSH6 D1145V V1192IHumanHPRTMT1 cellsN-Methyl-N′-nitro-N-nitrosoguanidine94043010( 18)
hMSH6 Het C1453T, Q485X; Het G3907A, A1303THuman500 kb (exons of protein kinases)PD1487aTemozolomide100047000This study
hMSH6 Hom delG2425, V809XHuman500 kb (exons of protein kinases)PD1489aTemozolomide and BCNU97755030This 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.