Abstract 4798: CpG island methylator phenotype (CIMP) in Puerto Rican Hispanic colorectal cancer patients
Authors: Bernabe-Dones Raul D. , Cruz-Correa Marcia R. , Castro Cristina I. , Lacourt Mercedes Y. , Rodriguez Heriberto , Castillo Xiomara M. , Marcano Isabel C. , Nunez Cristina , Baez Noelia , Lozada Maria E. , Maldonado Meredid S. , Oliveras Luis F. , Cardona Alberto 
Published: June 2012

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 CIMP hypermethylation is an important epigenetic change associated with gene silencing, poor prognosis and lower response to chemotherapy in CRC patients. However, prevalence of CIMP status and specific clinicopathological features has not been examined in Puerto Rican Hispanic CRC patients. In this pilot study we determined the CIMP status in PR Hispanics with CRC and examined its association with phenotypical characteristics.

Methods: Methylation-specific PCR (MSP) was used to evaluate DNA methylation in eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, hMLH1, p16) gene in forty-six 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. Clinicopathological characteristics were correlated with CIMP status using Wilcoxon rank tests, Chi square and Fisher exact t-tests, as appropriate using STATA 10.0.

Results: Forty-six CRC cases (mean age at diagnosis 62.1 ± 11.5 years; 21 males) were evaluated. Tumors were mostly located in the distal colon (85.4%), were moderately differentiated (65.1%) and were Dukes Stage B/C (90.0%). Two percent (1/46) of CRC cases were CIMP-High; 74.5% (35/46) were CIMP-Low; and 23.4% (11/46) were No-CIMP. IGF2 (53.2%) and p16 (36.2%) were the two most commonly methylated genes. CIMP-High/Low tumors were more common among women and among individuals ≥ 60 y/o (borderline statistical significance). There were no significant statistical associations between CIMP status and tumor staging, differentiation, tumor location or survival.

Discussion: We report for the first time CIMP status in Puerto Rican Hispanics with CRC. CIMP-hypermethylation may be less frequent among Hispanics than previously reported in other racial and/or ethnic groups, with a discrete clinicopathological phenotype and gene methylation pattern. Understanding epigenetic silencing by methylation of promoter regions of the CpG islands 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 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4798. doi:10.1158/1538-7445.AM2011-4798