The SNV pattern induced by TMZ in MSH2-/- line closely resembles signature SBS11 (Figure 5B and Supplementary Figure S4), which was initially derived from TMZ-treated cancers (1) and later demonstrated to result from a combination of TMZ treatment and MMR deficiency selected as a TMZ resistance mechanism (64). This evidence concerns the gene MSH2 and hyperinsulinemic hypoglycemia, familial, 4.