Genetics Analysis of Gastric Cancer Metastasis to the Peritoneum

Nazanin Nourbehesht1,2, Robert Eveleigh2, Ugo Mancini3, Madeleine Arseneault1,2, Lorenzo Ferri3, Yasser Riazalhosseini1,2

1. Department of Human Genetics, McGill University, Montreal; 2. McGill University and Genome Quebec Innovation Centre, Montreal; 3. Department of Surgery, McGill University, Montreal

Gastric cancer is one of the leading causes of cancer related death worldwide accounting for over 2000 deaths/year in Canada. Peritoneal metastasis is the most common site of gastric cancer progression after curative intent surgery and is the leading cause of death. Metastasis to this site represents a significant challenge in management due to the current scarce knowledge about the underlying factors. We have performed Whole-exome sequencing of patient-matched trio samples including normal DNA, primary gastric cancer and peritoneal metastasis from five unrelated patients in order to identify somatic mutations associated with peritoneal metastasis. We found several genes recurrently mutated in peritoneal metastasis cancers. This data list consists of known cancer-related genes involved in tumor recurrence and metastasis including KRAS, TP53 and CDH1. Moreover, our analysis revealed additional genes some of which have recently been reported in gastric cancer by other NGS studies including SPTA1 and HMCN1 and genes coding for FAT cadherins, and members of ephrin receptor signaling. Our findings provide the first catalogue of somatic mutations in peritoneal metastasis of gastric cancer.