Unique mutational profile associated with a loss of TDG expression in the rectal cancer of a patient with a constitutional PMS2 deficiency

► We characterized the mutator phenotype of a very early onset rectal cancer. ► High frequency of C:G>T:A or G:C>A:T transitions at methylated CpG sites was found. ► A somatic TDG mutation was found associated with TDG expression loss in the tumor. ► 1st in vivo evidence that TDG acts against deleterious 5-methylcytosine deamination.