Beyond CDH1 Mutations: Causes of Hereditary Diffuse Gastric Cancer

Since highly penetrant CDH1 mutations were described in hereditary diffuse gastric cancer, such mutants have attributed to roughly 40 % of cases. However, the molecular basis of the remaining 60 % of families, defined by clinical parameters, remains to be determined. Significant advances in sequencing technologies in the past several years have improved all aspects of gene discovery; including accuracy and analysis of data, speed with which data is analyzed and the overall cost of sequencing. Specifically, progress in high-throughput methodologies that allow for more targeted sequencing of interesting genes, along with the ability to sequence many samples in a single run, account for considerable breakthroughs made in hereditary disease research, including hereditary diffuse gastric cancer. To this day, CDH1 remains the most significant gene attributing familial patterns of diffuse gastric cancer. However, by utilizing the latest next generation sequencing technologies and examining non-CDH1 carrying families, researchers hope to identify the remaining gene(s) attributing to these cases at a faster and more efficient rate.