Hannah Rymen

Pathogenic germline variants in the DNA damage response gene BRCA2 are strongly associated with an increased risk of developing breast, ovarian, pancreatic, and prostate cancers. However, diagnostic testing of individuals with a suspected hereditary cancer predisposition frequently identifies variants of unknown significance (VUS) in BRCA2. For carriers of these VUS, available clinical evidence and in vitro functional assays often provide insufficient information to accurately assess cancer risk. Moreover, not all pathogenic variants in BRCA2 carry the same level of disease risk. For these hypomorphic or reduced-penetrance variants, there is an urgent need for cost-effective in vivo models. This uncertainty complicates decisions regarding risk-reducing interventions, targeted treatments and presymptomatic testing for family members.
The general aim of this project is to develop a cost-effective, efficient in vivo model for the functional characterization of BRCA2 variants. To knock-in variants in the zebrafish genome CRISPR-mediated prime editing will be used and subsequently their pathogenicity will be tested using different functional readouts in the F2 generation. Additionally, this project aims to evaluate whether hypomorphic BRCA2 variants can be modeled in vivo in zebrafish to determine if their phenotypes are distinguishable from highly penetrant loss-of-function and neutral variants, and to assess whether these variants are associated with delayed tumor formation.  Lastly, we will further expand our functional assays with a readout that can be performed at an earlier F0 generation.
This will contribute to accurate classification of VUS in BRCA2 and lead to more adequate genetic counselling, clinical and therapeutic management of cancer patients and their relatives.
 

I obtained my degree, Master in Biomedical Sciences, at Ghent university in 2025. My master thesis was also performed in the lab for cancer predisposition and precision oncology with prof. Claes as my promotor. The goal of my research was to knock-in and functionally evaluate BRCA2 missense variants in the zebrafish. After graduating, I joined the lab of Kathleen Claes as a full-time doctoral fellow.
 

• Lab address: Center for Medical Genetics, Medical Research Building 1, Ghent University Hospital (entrance 34), Corneel Heymanslaan 10, 9000 Gent, Belgium
• Website Lab Claes
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• Hannah Rymen is interested to receive invitations for presentations or talks