MAIN OBJECTIVE
With the increased use of genetic sequencing to inform clinical decision-making in oncology, the possibility of identifying clonal hematopoiesis (CH) in the setting of genomic analysis is increasingly likely. The major aim of the HIPNOSE proposal is to evaluate the presence of CH-related mutations in genes relevant for pancreatic ductal adenocarcinoma (PDAC) in plasma cfDNA and tumor tissues from patients with locally advanced and metastatic PDAC and to evaluate the clinical significance of CH-related mutations on the interpretation of liquid biopsy/tumor sequencing results. The same ultradeep targeted NGS platform will be applied across all three sources of DNA to detect mutations with low variant allele frequency in the corresponding tissue, plasma, and peripheral blood cells (PBC) samples. Mutations detected from PBCs will be categorized as CH-related mutations. We will then apply the same ultradeep targeted NGS platform on PBC samples from healthy controls matched by age and gender to determine if those variants have functional significance or they represent biological noise. A cohort of locally advanced/metastatic PDAC patients will be prospectively set-up and used for validation of the previously identified mutations using digital droplet PCR.