In these patients, the signature 11 mutation loads in metastatic disease were coincident with predicted deleterious mutations in DNA-mismatch repair genes, including MSH6 (CAS-G and SK-H), MLH1 (CAS-G), MLH3 (CAS-G and SK-H) and MSH3 (SK-H); mutations in CAS-G were validated by targeted amplicon sequencing (Supplementary Table 3). This evidence concerns the gene MLH3 and metastatic neoplasm.