Abstract

Abstract We have identified DNA methylation biomarkers that discriminate patients with colon cancer from patients without colon cancer using array-based profiling methods. Most DNA-based biomarkers for colon cancer rely on the detection of cancer cell-specific or cancer cell-prevalent mutations or DNA methylation changes in small numbers of tumor cells or small amounts of tumor cell-free DNA that are present in stool or lavage samples. Our hypothesis is that an individual's cancer-predisposing exposure history is recorded in normal tissues as “field cancerization”-related DNA methylation changes and that these changes will be present in normal colon, as well as other normal tissues, including peripheral blood. Consistent with the notion of changes based on “individual exposure history”, the bulk of the candidate biomarkers identified are genes involved in carbohydrate and lipid metabolism, as expected from epidemiological associations between colon cancer and “western” diets. We have now validated that our candidate methylation biomarkers are effective at discriminating cancer patients from controls using normal colon tissue from an independent population, and irrespective of whether the patients have left-side or right-side cancers. We have also found that a significant fraction of our candidate biomarkers also discriminate cancer patients from controls, using peripheral blood DNA analyzed by bisulfite pyrosequencing. Citation Format: Carmen Sapienza, May M. Truongcao, Jayashri Ghosh. Evaluation of methylation biomarkers for colon cancer using normal tissues. [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 2951. doi:10.1158/1538-7445.AM2015-2951

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