(465b) Utility of DNA Capture Resins in the Development of Minimally Invasive Tools for Genetic Monitoring of Pancreatic Health

Authors: 
Hilmer, A. J., Stanford University
Khosla, C., Stanford University
Park, W., Stanford University Medical Center
Jeffrey, R. B., Stanford University Medical Center

The diagnosis of pancreatic cancer carries an especially grim prognosis, with a median patient survival of less than 6 months, and an average 5-year survival of <5%.  One reason for this poor outlook is the fact that pancreatic cancer is often diagnosed very late in the cancer development, resulting in the existence of distant metastases in more than one-half of patients at the time of diagnosis.  There is a significant need for effective ways of detecting this cancer, early in its progression, which could lead to the evaluation and identification of better treatments for this deadly disease.  Because ~95% of pancreatic cancers are exocrine in nature, pancreatic fluid represents a rich source of potential biomarkers that could lead to earlier diagnoses, and better clinical outcomes.  However, the only method that is currently available for sampling pancreatic fluids is endoscopy, which is both time-consuming and highly invasive.

We are engineering a tool that would allow for the sampling and genetic screening of pancreatic fluids in a minimally invasive manner.  We have identified materials that efficiently capture DNA from raw, untreated pancreatic fluid, thereby allowing it to be purified for downstream analysis.  We have also performed time-course studies to evaluate fluctuations in pancreatic fluid DNA content upon secretin-stimulated secretion.  These samples are now being utilized, in conjunction with next-generation sequencing, to identify resident genetic mutations.  Here, I discuss these results and also provide data on our ability to detect rare mutant alleles within these fluid samples.