Abstract LB-003: Racial differences of intron retention and DNA methylation in breast cancer

Abstract

Abstract Regulation of gene expression by DNA methylation in gene promoter regions is well-studied; however, the effects of methylation in the gene body (i.e., exons and introns) on gene expression are comparatively understudied. Recently, hyper-methylation has been implicated in the inclusion of alternatively spliced exons; moreover, exon recognition can be enhanced by recruiting the methyl-CpG-binding protein (MeCP2) to hyper-methylated sites. In this study, we examined whether or not the level of methylation of an intron is correlated with how frequently that intron is retained during splicing using DNA methylation and RNA sequencing data from breast cancer tissue samples in The Cancer Genome Atlas (TCGA). We found that hypo-methylation of introns is correlated with higher levels of intron expression in mRNA and that most novel cancer-specific mRNA isoforms are due to intron retention. The methylation level of an intron is inversely correlated with its retention in mRNA transcripts from the gene in which it is located. Furthermore, we observed significant racial differences in the methylation level of retained introns: In samples from African-American donors, retained introns were not only less methylated compared to Caucasian donors, but also were more highly expressed. This underscores the need for Understanding racial epigenetic differences and their correlation with breast cancer is an important step toward achieving personalized cancer care. Citation Format: Dongwook Kim, Manu Shivakumar, Youngji Lee, Olufunmilayo Olopade, Dokyoon Kim, Younghee Lee. Racial differences of intron retention and DNA methylation in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-003. doi:10.1158/1538-7445.AM2017-LB-003