DNA methylator and mismatch repair phenotypes are not mutually exclusive in colorectal cancer cell lines

A potential link between DNA repair and de novo methylation of exogenous se quences in colorectal cancer cell lines suggested that cells deficient in m ismatch repair (MMR-) had an increased ability to silence the introduced vi rus promoter by DIVA methylation due to the presence of a methylator phenot ype (MET+) (Lengauer et al., 1997a), We explored this relationship in more detail and found that although there was a clear difference in the abilitie s of MMR cells to express the viral promoter compared to their MMR- counter parts, this difference was not consistently explained by levels of methylat ion in the viral promoter. Furthermore, we were unable to distinguish diffe rences between the levels of methylation of six endogenous known CpG island s or 100 random DNA fragments containing CCGG sites within the cells. No co nsistent differences between the abilities of the cells to methylate the Cp G island in exon 2 of the p16 gene were observed after transient demethylat ion by 5-aza-2'-deoxycytidine nor in the levels of expression of three huma n methyltransferase enzymes. Our results do not therefore support the exist ence of mutually exclusive DNA methylation (MET) and DNA repair (MMR) pheno types.