Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V45
Höfundar / Authors: Regína Lind Guðmundsdóttir1,2,3, Katrín Kristjánsdóttir 1,2,3, Sif Traustadóttir 1,2,3, Eydís Bergman1,2,3, Bjarni A. Agnarsson1,2, Aðalgeir Arason1,3, Rósa Björk Barkardóttir1,3, Bylgja Hilmarsdóttir1,2,3
Starfsvettvangur / Affiliations: 1. Pathology Department, Landspitali University Hospital, 2. Faculty of Medicine, University of Iceland, 3. Biomedical Center, University of Iceland.
Kynnir / Presenter: Regína Lind Guðmundsdóttir
Mutations in BRCA1 are known to cause hereditary cancer, primarily breast- (BC) and ovarian cancer (OC). BRCA1 deficient tumors are sensitive to PARP inhibitors and platinum therapy, however not all eligible patients benefit from this treatment and resistance will emerge over time. The BRCA1 c.4096+3A>G mutation, found in 1 in 500 Icelanders, and has been shown to increase the risk of OC and BC. Rather than causing the loss of the protein, BRCA1 c.4096+3A>G affects splicing by reducing the expression of the full-length protein and increases the expression of shorter BRCA1 isoforms. Whether tumors with the mutation show reduced sensitivity to targeted treatment is unknown. The aim of this project is to study how expression of the shorter BRCA1 d11q isoform impacts drug sensitivity and phenotype of BC (T47D) and OC (SNU-251) cell lines. CRISPR/Cas9 and lentiviral transduction was used to modulate BRCA1 expression. In addition, BRCA1 expression was studied in cell lines and OC and BC tissue samples. Results showed that shorter BRCA1 isoforms reduced sensitivity of cells to PARP inhibitors compared to BRCA1 knock out cells. Differential expression of BRCA1, and other proteins involved in DNA damage repair, was shown in cells lines and patient tissue with distinct BRCA1 isoform expression. Further work aims to deepen our understanding of how BRCA1 splice variants impact drug sensitivity of OC and BC and shed light on potential difference between of these cancer types.