Abstract B41: Methylome profiling identifies unique patterns of DNA methylation in endometrial cancers

Abstract

Abstract Introduction: DNA methylation is a stable epigenetic mark often perturbed during carcinogenesis. Growing evidence demonstrates a role for DNA methylation both as a regulator of gene expression and as a potential biomarker. Widespread accumulation of methylation in regulatory elements in certain cancers (termed the CpG island methylator phenotype) may play a role in carcinogenesis. Few studies, however, have investigated genome-wide methylation in a clinical cohort, as the methodology for analyzing these large datasets remains poorly developed. Endometrial cancer is the most common female gynecological cancer in the US, with sporadic endometrioid as the predominant subtype. Methods: This study profiles the methylomes of 76 sporadic endometrioid endometrial primary tumors and 12 normal endometrium using sequenced methylated fragments captured by the MBD protein (MethylCap-seq). Results: Analysis of bulk methylation in promoter CpG islands (CGI) identified a subset of tumors with a putative methylator phenotype. We are currently developing a gene signature to more easily detect endometrial tumors with a methylator phenotype, perform cross-platform analyses, and further characterize clinicopathological variables associated with the phenotype. We have also developed a pipeline for quality analysis and show that exclusion of poor quality samples increases statistical power to call differential methylation and reduces analysis artifacts. Conclusion: The results of our study highlight MethylCap-seq as a useful tool for profiling methylation patterns in large clinical datasets. Citation Format: Michael P. Trimarchi, Pearlly S. Yan, Kun Huang, Joanna Groden, Ralf Bundschuh, Paul J. Goodfellow. Methylome profiling identifies unique patterns of DNA methylation in endometrial cancers. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B41.