Abstract B14: Use of DNA methylation in circulating free DNA as a potent biomarker for pancreatic cancer detection

Abstract

Abstract Pancreatic cancer is highly lethal malignancy despite the recent clinical advancement. Since pancreatic cancer is often difficult to diagnose, there is an urgent need to develop novel biomarkers for early detection with blood tests. Epigenetic alterations have emerged as a common hallmark of many types of human cancers as well as pancreatic cancer. Studies have shown that epigenetic dysregulation is associated with multiple steps during carcinogenesis. Therefore, invention of blood-based DNA methylation biomarkers and their high-sensitive detection system may be a promising diagnostic tool for pancreatic cancer. In order to establish the diagnostic system, first, we performed genome-wide DNA methylation analysis of 38 EUS-FNA specimens of pancreatic cancer with clinical stage III-IV using Illumina Infinium HumanMethylation450 BeadChip. We further analyzed the DNA methylation profiles of other types of tumors in the public database, TCGA (The Cancer Genome Atlas), and identified five marker genes, which were specifically methylated in pancreatic cancers. In addition, analysis of DNA methylation status of pancreas cancers comparing 10 normal tissues in TCGA data set revealed that 99% of tumors were methylated at least one of the five markers (sensitivity, 98.9%; specificity, 44%). We next examined the DNA methylation status in the markers in the validation cohort (n=19) by bisulfite pyrosequencing and quantitative methylation specific PCR and found that 18/19 (95%) cases were methylated in at least one marker (AUC=0.95). Currently, our preliminary data showed that more than 95% of cancer patients have aberrant DNA methylation in circulating free DNA (cfDNA). Our results indicate that detection of DNA methylation in the cfDNA might be a promising and potent tool for diagnosis of pancreatic cancers. Citation Format: Keiko Shinjo, Yutaka Kondo. Use of DNA methylation in circulating free DNA as a potent biomarker for pancreatic cancer detection. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B14.