Abstract 160: CpG island methylator phenotype (CIMP) and P53 methylation patterns in Puerto Rican Hispanic colorectal cancer patients

Abstract

Abstract Introduction: The CpG island methylator phenotype (CIMP) with extensive promoter methylation seems to be a distinct epigenotype of colorectal cancer (CRC). CIMP hypermethylation blocks transcriptional activation of several genes associated with tumor suppression, cell cycle, DNA repair, differentiation and apoptosis. Moreover, the promoter CpG island hypermethylation is an important epigenetic change associated with gene silencing, poor prognosis and lower response to chemotherapy in CRC patients. However, specific clinical and pathologic features have not been associated with CIMP status in Puerto Rican Hispanic CRC patients. In this pilot study we determined the CIMP status and the methylation pattern of P53 gene in CRC to establish a possible correlation between aberrant methylation and clinicopathological characteristics. Methods: We employed methylation-specific PCR (MSP) to evaluate DNA methylation in eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, hMLH1, p16) and the methylation pattern of the tumor suppressor gene P53 in twenty-five CRC cases. No CIMP status was defined as no methylated locus, CIMP-Low status as one to three methylated loci, and CIMP-High status as four or more methylated loci. In addition, clinicopathological and methylation patterns were correlated to the CIMP status using Wilcoxon rank tests, Chi square and Fisher exact t-tests, as appropriate using STATA 10.0. Results: Twenty-five CRC cases (mean age at diagnosis 64.2 ± 11.7 years; 11 males) were evaluated. Tumors were mostly located in the distal colon (76.2%), were moderately differentiated (88.8%), and were Dukes Stage B/C (86.7%). Twelve percent (3/25) of CRC cases were CIMP-High, 80% (20/25) were CIMP-Low and 16% (4/25) were No-CIMP. Aberrant methylation was not detected in the tumor suppressor gene P53. There were no significant statistical associations between CIMP status and age at diagnosis, gender, tumor staging, differentiation, tumor location or survival. Discussion: This pilot study is the first work to evaluate the CIMP status in Puerto Rican Hispanics CRC patients. CIMP is a distinct epigenotype of colorectal cancer, and may be less frequent among Hispanic patients than previously reported in other racial and/or ethnic groups. Understanding epigenetic silencing by methylation of promoter regions of the CpG island will enable understanding of the colorectal tumorigenesis in Hispanic patients that may help tailor screening and therapeutic strategies for Hispanic patients. Current efforts are underway to characterize a large number of Puerto Rican Hispanics CRC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 160.