Genetic aberrations in Chinese pancreatic cancer patients and their association with anatomic location and disease outcomes

Abstract

Abstract Objectives Pancreatic cancer (PC) is one of the most lethal malignancies with an increasing death rate over the years. We performed targeted sequencing and survival analyses on 90 Chinese pancreatic cancer patients, hoping to identify genomic biomarkers associated with clinical outcomes and therapeutic options. Method Genomic DNA was extracted from formalin‐fixed paraffin‐embedded (FFPE) tissue specimens of 90 pancreatic cancer patients and sequenced. The associations with clinicopathological factors were analyzed. Result High prevalence of driver mutations in KRAS, TP53, CDKN2A, SMAD4, and ARID1A genes were found. Most mutated genes in PC belonged to cell cycle and DNA damage repair pathways. Tumors that arise from the pancreas’ body and tail (BT tumors) displayed a higher ratio of mutated KRAS and TP53 than those that arise from the pancreas’ head and neck (HN tumors), who showed less diverse KRAS subtypes. Patients with a KRAS p.G12R mutated tumor tended to have a prolonged disease‐free survival (DFS) and overall survival (OS) than other KRAS subtypes. Those with an altered ARID1A gene and more than two mutated driver genes tended to have a shorter DFS and OS. Conclusion HN and BT tumors of the pancreas displayed different mutational profiles, which had prognostic significances and indicated different potential therapeutic options.

Keywords

• body and tail of pancreas
• disease‐free survival
• DNA Damage Repair pathway
• head and neck of pancreas
• KRAS subtype
• overall survival