THE ROLE OF ARID1A IN GASTRIC TUMORIGENESIS AND TUMOR DEVELOPMENT

Abstract

Gastric cancer is the third leading cause of cancer deaths and the fifth most common cancer in the world. Various studies, including our own, have reported that ARID1A is frequently mutated or deleted in gastric cancer. Many studies have also shown that ARID1A is a tumor suppressor gene and it is frequently inactivated in a variety of cancer types. However, the mechanism of cancer development following the inactivation of ARID1A is not well studied, especially in the context of gastric cancer. As a result, the functional roles of ARID1A in gastric cancer development are not well understood and there are limited therapeutic opportunities that may be employed to specifically target ARID1A-mutant cancers. Therefore, this project seeks to further characterize the functional consequence of ARID1A mutations in gastric cancer through sequencing genome and epi-genome of patient samples and isogenic ARID1A knockout gastric lines. It profiles genome and epigenome abnormality in ARID1A mutated samples and reveals several altered pathways and dysregulated genes. The most universal pathway is ultra-activated cell cycle related pathways, although the most activated gene might be subject to the difference in individual genetic background.