Aside from secondary mutation of MSH3 in the setting of an MSI-H colorectal cancer caused by frameshift of its [A8] microsatellite, there has been no example in the literature for: (a) germline mutation for MSH3 for which to study its consequences; (b) evidence for somatic inactivation of MSH3 (aside from MSI-H cancers) for which MSH3 function could be lost; or (c) epigenetic inactivation of MSH3 (such as that seen for MLH1). This evidence concerns the gene MLH1 and colorectal cancer.