Exocrine pancreas-derived DNA in plasma as a potential diagnostic tool in pancreatic-cancer

Roni Ben Ami ^1,2,3 Brian M. Wolpin ⁴ Benjamin Glaser ⁵ Ruth Shemer ³ Yuval Dor ³

¹Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, the Hebrew University-Hadassah Medical School, Israel
²Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Israel
³Department of Developmental Biology and Cancer Research, The Hebrew University-Hadassah Medical School, Israel
⁴Dana-Farber Cancer Institute, Harvard Medical School, USA
⁵Endocrine Service, Hadassah-Hebrew University Medical Center, Israel

Pancreatic ductal adenocarcinoma (PDAC) presents with advanced, incurable disease in over 80% of patients. Diagnosis at an earlier stage greatly improves patient survival. Molecular testing of plasma-derived circulating cell-free DNA (cfDNA) released from the tumor is a promising tool for both early and non-invasive diagnosis. We used comparative methylome analysis to identify 10 methylation haplotype blocks that serve as highly specific biomarkers for exocrine pancreas-derived DNA. We evaluated pancreas-specific methylation in cfDNA using bisulfite-treated DNA and amplicon-based next-generation sequencing, and discovered sensitive and specific identification of exocrine pancreas cfDNA in patients with pancreatic cancer compared to healthy controls. Ongoing studies examine assay sensitivity in patients with early stage PDAC and patients with pre-malignant lesions.