The Genomic Alteration Landscape of Pancreatic Duct Adenocarcinoma

Abstract

By 2030, PDAC is projected to be the second leading cause of cancer-related death in the US. PDAC is a multifactorial disease driven by genomic alterations. Understanding this alteration landscape will both refine the knowledge of disease etiology and enhance disease stratifications, drug design, and targeted treatment. This study aimed to identify novel genetic alterations that are associated with pancreatic cancer biology and prognosis to further refine the genetic focus for therapy development, disease subtyping, and risk assessment in PDAC. To this end, SNV, CNV, and clinical data for PDAC patients were downloaded from the ICGC data portal and analyzed for somatic mutations and recurrent copy number variations. This study showed that KRAS, TP53, and TTN are not only highly mutated but also associated with poor survival in PDAC. Also, this study showed that CN-LOH TP53, KRAS, SMAD4, and RYR3 were associated with reduced risk of death from PDAC.