Introduction: Detection of quantitative and qualitative changes in cell-free, tumor-derived nucleic acids in cancer patients are being evaluated as potential screening, monitoring and diagnostic tools. Genetic and epigenetic changes in cell-free plasma DNA (cfpDNA) have been studied as non-invasive colorectal cancer (CRC) diagnostic markers, but a gene panel with the diagnostic accuracy necessary for clinical use has not been defined. The CpG island methylator phenotype (CIMP), characterized by hypermethylation in promoter-associated regions, is one of the molecular mechanisms resulting in CRC. We evaluated the detection of promoter hypermethylation in a gene panel previously used to define CIMP in CRC tumors, as plasma biomarkers. Methods: Methylation specific PCR was used to analyze eight CIMP-specific gene promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, hMLH1, p16, CRABP1) in cfpDNA. Forty age-and-gender matched plasma samples (20 CRC and 20 controls) were evaluated. Samples were classified as methylated, unmethylated or not detected if not amplified by either primer set. Results: Methylation patterns of eight genes in 40 subjects (20 CRC and 20 controls; mean age 67 ± 12.2 years; 20 females) were examined. Five genes revealed a 100% unmethylation pattern. p16 was found to be more likely methylated in controls (11%) whereas NEUROG1 and CRABP1 were more likely to be methylated in CRC cases (6% and 33%, respectively). 53.3% of CRC and 48% controls had β1 methylated genes (OR = 1.24, 95% CI 0.34-4.46). The use of β1 methylated genes detected CRC with 40% sensitivity and 65% specificity. Discussion: We report the first evaluation of the methylation pattern of an eight-gene panel as CRC biomarkers in Hispanics. Our preliminary findings showed that genes were mostly unmethylated in cases and controls. NEUROG1 and CRAP1 were found to be most likely methylated in CRC patients, but the diagnostic accuracy of this panel was poor as a CRC screening biomarker.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2086. doi:1538-7445.AM2012-2086