Targeted Sequencing of Pancreatic Ductal Adenocarcinoma Tissue

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer and the majority of patients present with metastatic disease. Metastatic spread requires a reorganisation of the actin cytoskeleton, a process that is dependent on the Rho family GTPases and their interaction with subsequent downstream effectors. The p21 activated kinases (also known as the PAKs) are effectors of Rho GTPases Cdc42 and Rac and play key roles in cell migration and survival. PAK4 is overexpressed in PDAC and can reciprocally activate the PI3K pathway. Hepatocyte growth factor (HGF), via c-Met, is an established activator of PAK4 and the PI3K pathway and may promote PDAC invasion. Next generation sequencing (NGS) was performed on 31 PDAC tissue using a pre-determined targeted panel to attempt to identify novel mutations in the PAK: PI3K pathway. Targeted NGS identified several recurrent mutations including 5 PAK4 mutations in PDAC tissue.