Maya berlinger '16

Title: Proving the Synthetic Lethal Interaction Between ARID1A and EZH2 in Hepatocellular Carcinoma

Hypothesis: The inhibition of EZH2 in ARID1A-mutant HCC cell lines will cause cell death, proving that there is a synthetic lethal interaction between the two genes.

Activities and Interests: Cross Country, Winter and Spring Track, French Club, Model UN, member of NHS, member of French Honor Society, STAT, Girl Scouts, Culture Club, Chem Club President


Abstract: Liver cancer, of which the most common form is hepatocellular carcinoma (HCC), is one of the leading causes of cancer deaths worldwide. Owing to its limited treatment options, HCC has a very poor prognosis. Currently, research is being done on therapies based on selective targeting, an example of which is synthetic lethality. Synthetic lethality describes a relationship between two genes in which the mutation or deletion of one gene is not lethal to the cell, while the alteration of both genes is lethal. A previous study established the synthetic lethal interaction between the genes ARID1A and EZH2 in ovarian cancer. Since ARID1A is frequently mutated in HCC, affecting up to 13% of all patients, this project sought to determine if ARID1A and EZH2 had a synthetic lethal interaction in HCC as well. To address that aim, EZH2 activity was inhibited through GSK126, a small molecule inhibitor, in both ARID1A-mutant and ARID1A wild type HCC cell lines. There was no clear sensitivity to EZH2 inhibition in ARID1A-mutant HCC cell lines, indicating that no such relationship exists in HCC.