Specific Variants in the MLH1 Gene Region May Drive DNA Methylation, Loss of Protein Expression, and MSI-H Colorectal Cancer
Figure 1
Proposed model for genetic susceptibility to DNA methylation in sporadic MSI-H CRCs.
Specific SNPs predispose the region, including the MLH1 gene promoter, to methylation, which results in promoter silencing and loss of MLH1 gene expression that is measured by immunohistochemical staining. Loss of the MLH1 gene expression leads to genome-wide microsatellite instability and MSI-H colorectal cancer.