Discovery and Validation of a TP53 Synthetic Lethal Interaction In RKO Colon Cancer Cells

School Name

Governor's School for Science & Mathematics

Grade Level

12th Grade

Presentation Topic

Cell and Molecular Biology

Presentation Type

Mentored

Mentor

Mentor: Phillip Buckhaults, University of South Carolina

Written Paper Award

4th Place

Abstract

While some treatments have been developed in order to combat cancer, most of them involve harming benign cells as well as cancerous cells. In order to only target mutated cells, we tested the application of synthetic lethality. TP53 a gene that plays a major role in regulating the cell cycle, which is why it is often mutated in cancerous colon cells along with other types of cells. Synthetic lethality occurs when two genes that are otherwise dispensable individually cause cell death when mutated together. Because many types of cancers have a knocked out TP53 gene, the need for synthetic lethality between TP53 mutation and some other gene to be discovered exists. In our case, the gene that was synthetic lethal with TP53 was a gene present in the SHH pathway. We found that by inhibiting the SHH pathway, which in turn would inhibit the gene in cells with the drug cyclopamine, only the cells with a TP53 mutation (the cancerous cells) were inhibited. The normal cells remained active opposed to their cancerous counterparts. The results support the possibility of cyclopamine being used as a drug to help treat patients with TP53-mutant colon cancers without harming normal cells. Synthetic lethality can be used on other cancers with TP53 mutations.

Start Date

3-25-2017 11:59 PM

Presentation Format

Written Only

Group Project

No

COinS
 
Mar 25th, 11:59 PM

Discovery and Validation of a TP53 Synthetic Lethal Interaction In RKO Colon Cancer Cells

While some treatments have been developed in order to combat cancer, most of them involve harming benign cells as well as cancerous cells. In order to only target mutated cells, we tested the application of synthetic lethality. TP53 a gene that plays a major role in regulating the cell cycle, which is why it is often mutated in cancerous colon cells along with other types of cells. Synthetic lethality occurs when two genes that are otherwise dispensable individually cause cell death when mutated together. Because many types of cancers have a knocked out TP53 gene, the need for synthetic lethality between TP53 mutation and some other gene to be discovered exists. In our case, the gene that was synthetic lethal with TP53 was a gene present in the SHH pathway. We found that by inhibiting the SHH pathway, which in turn would inhibit the gene in cells with the drug cyclopamine, only the cells with a TP53 mutation (the cancerous cells) were inhibited. The normal cells remained active opposed to their cancerous counterparts. The results support the possibility of cyclopamine being used as a drug to help treat patients with TP53-mutant colon cancers without harming normal cells. Synthetic lethality can be used on other cancers with TP53 mutations.