MLH1 and cancer: Supporting this hypothesis, we observed that in the lung—the tissue with the strongest association between MLH1 expression and C>T mutation load—samples with low expression of MLH1 had a significant resemblance to a cancer mutation signature that has been attributed to deficient MMR (Fig. 4d; similarity to COSMIC signature 6: cosine similarity = 0.76, p = 0.001 for C>T mutations, and cosine similarity = 0.28, p = 0.02 across all mutation types).