PO-183 Identification of differentially hypomethylated genes associated to metastasis behaviour in colorectal cancer

Introduction Colorectal cancer (CRC) is an important public health problem worldwide. In Chile, CRC is the fourth most frequent cancer and its incidence is rising. Sporadic CRC results from the accumulation of both acquired genetic and epigenetic changes that transform normal glandular epithelium into invasive adenocarcinoma. DNA methylation has an important role in colon carcinogenesis and also has been found involved in metastasis pathways of CRC. However, there are no studies that analysed whole genome in the search of specific methylated genes in metastasis of CRC, despite the next-generation sequencing platforms and methylation arrays available. Therefore, in this project it is proposed to find novel methylation markers of metastasis by comparing primary tumours and their corresponding lymph node metastasis, using a next-generation sequencing platform. The aim of this study was to identify differentially methylated genes associated with metastasis tumour behaviour in colorectal cancer. Material and methods Five paired FFPE samples of CRC primary tumour and its corresponding lymph node metastasis were analysed with genome-wide Methyl-Seq bisulfite sequencing. Five differently hypomethylated genes were selected using bioinformatics tools. Bioinformatic analysis was realised comparing colorectal primary tumour vs lymph node metastasis using methylKit tool. Results and discussions A total of 196 genes were detected as differentially methylated in their promoter region, 94 of which were hypomethylated on lymph node metastasis group. CS , RNF130 , HERC6 , ZNF717 and RNF216-IT1 genes presented differences over 50% in their methylation status, compared with CRC primary tumours group. According to their ontology, these genes are involved on regulation of tricarboxylic acid cycle, transcription, carbohydrate metabolic process and protein polyubiquitination. Conclusion CS , RNF130 , HERC6 , ZNF717 and RNF216-IT1 genes were found hypomethylated in colorectal metastasis compared to primary tumour. These genes could be implied in metastasis behaviour in colorectal cancer, but further studies are necessary to evaluate their functions.