Abstract
Abstract
Background: Colorectal cancer (CRC) involves epigenetic changes including DNA hypomethylation, a paradigm shift in the role of DNA methylation alterations in colorectal carcinogenesis.
Aim: Here we performed Reduced Representation Bisulfite Sequencing (RRBS) on a normal, and a tumor patient's tissue DNA to elucidate hyper- and hypomethylaed target genes in colorectal cancer progression in this population.
Methods: Genomic DNA was isolated from fresh frozen surgical tissues from a patient with normal colon, and from a carcinoma patient. RRBS was performed on these DNA samples for hyper- and hypomethylation targets identification. Alignment, mapping and CpG methylation analyses were performed. Preferential hypomethylated pathways were determined using Ingenuity Pathway Analysis (IPA).
Results: We identified the hyper (6360 CpG sites) and hypo-methylation (4845 CpG sites) status of top genes in the CpG Island within promoter regions (19 and 18 genes respectively). Top hyper- and hypomethylated CpG Island outside promoter regions (16 and 18 genes, respectively) were also identified. Among these top genes, CDH4 and SOX21 were reported to be hypermethylated in CRC and SCUBE2 (112 methylated CpG) mapped by IPA to the Hedgehog, TGF-β, and VEGF Signaling pathways was reported to play a role in breast cancer. Among the top hypomethylated genes, ACOT9 (97 CpGI sites) and RIN2 (40 CpGI sites) might play a significant role in CRC in AAs, since IPA mapped these markers to the Wnt/β-catenin, VEGF and PTEN signaling pathways. ACOT9 was found to play a role in breast cancer.
Conclusion: This work provides insight into differential CpG island hyper- and hypo-methylation profiles in CRC and provides a window into the more complex epigenetic events associated with CRC, including the hypomethylation of known and novel genes. Investigations into the possible roles of the novel gene targets in the context of early and prognostic methylation biomarkers are underway.
Citation Format: Hassan Ashktorab, Afnan Shakoori, Shatha Zarnogi, Xueguang Sun, Sudhir Varma, Edward Lee, Babak Shokrani, Adeinko O. Laiyemo, Kareem Washington, Hassan Brim. Whole genome hypo- and hyper-methylation sequencing among Africa American patients with colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4588. doi:10.1158/1538-7445.AM2015-4588