These alterations include methylation of CpG sites in the promoter region or first exons of tumor suppressor genes leading to transcriptional silencing.1 High levels of DNA methylation in tumor suppressor genes may be associated with a positive CpG island methylator phenotype (CIMP+) that can be either cancer-associated or age-related.2 CIMP+ is often found in tumors with microsatellite instability (MSI) caused by inactivation of the mismatch repair gene MutL Homolog 1 (MLH1). The gene discussed is MLH1; the disease is cancer.