At the 2023 Society of Gynecological Oncology’s Annual Meeting on Women’s Cancer in Tampa, Florida, Rebekah Peplinski, graduate research assistant and PhD candidate, University of Iowa, Iowa City, Iowa, discussed the potential role of Sleeping Beauty mutagenesis for understanding and identifying genes related to tumor progression in high-grade ovarian cancer.

Ms. Peplinski noted that identifying these oncogenic drivers could potentially aid in the development of treatments targeting the genes associated with tumor progression in high-grade ovarian cancer, with aims of lowering tumor burden and controlling disease progression in this patient population.

Transcript

Hi, my name is Rebekah Peplinksi. I am a graduate student at the University of Iowa, and I have been working on my project that is about tumor progression in high grade ovarian cancer. I'm here at the 2023 Society of Gynecological Oncology’s Annual Meeting on Women’s Cancer presenting on that topic.

High-grade ovarian cancer is a large portion of the ovarian cancer field. One of the large problems of high-grade ovarian cancer is that we don't necessarily have clear oncogenic drivers that are leading to tumor progression. With recent sequencing methods, we have seen large scale duplications and maybe deletions. However, those regions that are deleted are duplicated are, like I said, large. They include hundreds of different genes.

Being able to identify what genes are involved in that region that are leading to tumor progression – it's very unclear. In my project, we use a system called Sleeping Beauty mutagenesis, and that can create mutations throughout the genome, in a very controlled way, but they're very random. We can then sequence tumors and identify where these mutations are happening.

By being able to identify where these mutations are happening, we could potentially identify what these candidate genes are that are leading to progression. The overall goal there, once we've identified what those candidate genes are, is to be able to target them in some way, to control tumor progression. That would help women lower tumor burden or just control disease progression.

We found some candidate genes that look to be in line with the large-scale duplications. We have identified some candidates and then right now, and we're going forward with validating those. We're looking to express those alone in a mouse model. Once we do that, we can identify whether that increases progression or not. Once those candidates are validated, we could potentially collaborate with other scientists to try to develop some targeted therapy to reduce the tumor progression.

Ovarian cancer itself is very hard to treat. A lot of patients don't necessarily respond well to treatments, and it's often difficult to treat them. This could potentially bring a new avenue for not only how to treat them but maybe even how to stop the disease and could be curative. That's a cool avenue to explore.

Source:

Peplinski R. “Characterization of genetic mechanisms of ovarian tumor progression using sleeping beauty mutagenesis in vivo.” Presented at SGO Annual Meeting on Women's Cancer; March 25-28, 2023; Tampa, FL.