MLH1 and cancer: The tumor with the highest mutation burden was a carrier of a pathogenic BRCA1 variant (p.Asn1236Phefs) and harbored two-hit somatic inactivation of MLH1 through a truncating mutation (p.Ser170Argfs*20) coupled with loss of heterozygosity of chromosome 3p22.2 (Fig. 2), consistent with hypermutation seen in other cancers [33].