Abstract 1484: Genome wide study reveal microrna based methylation phenotype in oral cancer

Abstract Introduction: Oral cancer is one of the leading causes of cancer burden in India. Studies over the years have enforced the role of deregulated microRNA expression in oral cancer development and progression. Incidentally not much is known about the cause of microRNA deregulation or to what extent can it be attributed to methylation. Established genome wide microarray platforms like 450K Illumina Bead Chip have probes for very limited number of microRNAs along with restriction on distance of the probes from microRNA transcription start site. We have used genome wide methylation sequencing approach RRBS to get deeper insight on microRNA methylation. Aim: Genome wide methylation profile of 15 paired oral cancer and adjacent normal tissue was compared to generate a detailed map of microRNA methylation in oral cancer. The methylation results were further correlated to microRNA expression data generated on a subset of these samples. Methodology: RRBS based global methylation sequencing of 15 pairs of samples was conducted on HiSeq 2500 with an average 10X depth. Analyses were done using DMAP software. Previously generated TLDA based microRNA expression data was used for correlation analysis. Result: Similar to protein coding genes, microRNAs also showed methylation based clustering. Interestingly majority of methylation hits were more than 2kb upstream of miRNA transcription start site which is generally not considered in known microarrays. Distribution of hypo and hyper methylation sites is different across the various CpG features like cores and shelves as well as across chromosomes. MicroRNAs like mir-181c, miR-99b, miR-23a among others showed significant negative correlation between methylation frequency and expression level. IPA based pathway analysis emphasized repression of apoptosis and cell death pathways along with activation of cell proliferation and colony formation. Conclusion: Understanding the role of methylation in microRNA deregulation could help us detect and possibly prevent a chain of events, which lead to disrupted pathways eventually leading to cancer, at the onset. Note: This abstract was not presented at the meeting. Citation Format: Roshni Roy, Aniruddha Chatterjee, Navonil De Sarkar, Bidyut Roy. Genome wide study reveal microrna based methylation phenotype in oral 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 1484. doi:10.1158/1538-7445.AM2017-1484