Abstract
Abstract Background: Colorectal adenoma (CRA) to cancer (CRC) progression involves in epigenetic changes including DNA methylation. Here we performed whole genome Bisulfite Next-Generation sequencing (WGBSNGS) on a normal, a tubular adenoma and a tumor patients’ tissue DNA to elucidate epigenetic drivers in normal to cancer progression. Patients and Methods: Genomic DNA was isolated from fresh frozen tissues from a patient with normal colon, from a tubular adenoma lesion (<0.5 cm) and from a carcinoma. A WGBSNGS at >20X depth was performed on these DNA samples., Alignment, mapping and CpG methylation analyses were done. Pyrosequencing and immunohistochemistry (IHC) was used to confirm selected CpG methylation. Results: We identified 94 unique CpG sites hypermethylated in 4 novel genes in adenoma compared to normal and 180 unique CpG sites in 7 genes in cancer. Ingenuity pathway analysis (IPA) showed that the methylated genes including a novel gene ATXN7L1 were involved in WNT pathway, ubiquotlation process and cross-talk with B-catenin, in the adenoma. Three of the hypermethylated genes in cancer were, Loc100506436: a novel gene with 17 unique CpG sites (EGFR pathway, cRNA CpG site hypermethylated is part of MEK1/2), GPNMB with 7 unique CpG sites (a G protein) and TNFAIP2 with 8 unique CpG sites (its role was noted in Head and neck cancer). IHC confirmed the lack of expression in cancer. Conclusion: This work provides insight into differential CpG island methylation profiles in CRA, CRC vs. normal colon tissue and provides a window into the more complex factors, including alteration of known and novel genes as a multiple CpG methylation drivers in colorectal carcinogenesis. Investigations into the possible roles of the novel gene targets in the context of early and prognostic methylation biomarker are underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4521. doi:1538-7445.AM2012-4521
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
