title: Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients with microsatellite unstable colon cancer.
abstract: Serological tumor markers have proven valuable in the care of individuals with cancer for the early detection of primary cancers, early detection of cancer relapse, monitoring the response of cancers to therapy, and as predictors of cancer prognosis. Recently, the aberrant hypermethylation of the hMLH1 promoter and its consequent transcriptional silencing has been shown to be a common event in the formation of sporadic microsatellite unstable colon cancer. The silencing of hMLH1 expression appears to be controlled by the hypermethylation of a specific region in the hMLH1 promoter. We developed a methylation-specific PCR assay that assesses this region of the hMLH1 promoter. We found that this assay is able to detect methylated hMLH1 promoter DNA in the serum of some patients with microsatellite unstable colon cancers. In a panel of sera from 19 colon cancer cases, 9 with hMLH1 promoter methylation in the tumor primary, the assay proved 33% sensitive and 100% specific. This assay offers a potential means for the serum-based detection and/or monitoring of microsatellite unstable colon cancers.
authors.affiliation: Department of Medicine, Ireland Cancer Center, Case Western Reserve University, University Hospitals of Cleveland, Ohio 44106, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Grady
authors.forename: A
authors.initials: A
authors.lastname: Rajput
authors.forename: J D
authors.initials: JD
authors.lastname: Lutterbaugh
authors.forename: S D
authors.initials: SD
authors.lastname: Markowitz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002352:Carrier Proteins; D003110:Colonic Neoplasms / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1