distinct high-profile methylated genes in colorectal cancer明显的引人注目的甲基化基因在结直肠癌.pdfVIP

Distinct High-Profile Methylated Genes in Colorectal Cancer 1 2 2 1 Pooneh Mokarram , Krishan Kumar , Hassan Brim , Fakhraddin Naghibalhossaini , Mehdi Saberi- 1 2 3 3 2 2 firoozi , Mehdi Nouraie , Robert Green , Ed Lee , Duane T. Smoot , Hassan Ashktorab * 1 Department of Internal Medicine and Gastroenterology Research Center, Shiraz, Iran University of Medical Sciences, Tehran, Iran, 2 Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, D. C., United States of America, 3 Department of Pathology, Howard University, College of Medicine, Washington, D. C., United States of America Abstract Background: Mutations and promoters’ methylation of a set of candidate cancer genes (CAN genes) are associated with progression of colorectal cancer (CRC). We hypothesized that these genes’ promoters are inactivated through epigenetic silencing and may show a different profile in high-risk populations. We investigated the status of CAN gene methylation and CHD5 protein expression in African American CRC tissue microarrays (TMA) using immunohistochemical staining. Methodology/Principal Findings: The promoter methylation status of the CAN genes was studied by methylation-specific PCR (MSP) in 51 Iranians (a white population) and 51 African Americans (AA). Microsatellite instability (MSI) was analyzed as well. The differential frequency of methylation for each gene was tested by chi-square analysis between the two groups based on matched age and sex. CHD5 protein expression was evaluated in moderate to well differentiated and poorly differentiated carcinomas compared to matched normal