Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2017
Erindi/veggspjald / Talk/poster V27
Höfundar / Authors: Birna Þorvaldsdóttir (1), Beth A. Cimini (2), Morgan E. Diolaiti (3), Katrín Ólafsdottir (4), Jón G. Jónasson (4) , Elizabeth H. Blackburn (2), Jórunn E. Eyfjörð (1)
Starfsvettvangur / Affiliations: 1. Cancer Research Laboratory, BioMedical Center, University of Iceland, 2. Department of Biochemistry and Biophysics, University of California-San Francisco, 3. Department of Pathology, University of California-San Francisco and 4. Department of Pathology, Landspitali University Hospital
Kynnir / Presenter: Birna Þorvaldsdóttir
Germline mutations in the BRCA2 gene are associated with highly increased risk of breast cancer. The BRCA2 protein is essential for homologous recombination repair of damaged DNA, protection of stalled replication forks and has been shown to play a role in telomere protection and maintenance. Disruptions in telomere homeostasis can result in excessive telomere shortening and drive chromosome instability, a hallmark of BRCA2-related cancers.
The aim of the study was to measure and compare telomere length (TL) and levels of telomere dysfunction in tumor-adjacent normal breast tissue between BRCA2 mutation carriers and non-carriers in a well-defined group of Icelandic breast cancer patients.
TL was measured in paraffin-embedded normal breast tissue samples using Quantitative Fluorescence in Situ Hybridization (Q-FISH). The samples were also stained for the DNA double-strand break marker 53BP1 to assess telomere dysfunction induced foci.
Luminal epithelial cells showed the shortest TL and highest number of DNA damage foci of the cell types in normal breast tissue. This is highly relevant as these are the cells from which most breast cancers originate. No difference was detected in age-adjusted TL between BRCA2 mutation carriers and non-carriers. However, consistent with our recently published data from TL measurements in blood in the same study group, shorter TL is associated with earlier breast cancer occurrence in BRCA2 mutation carriers but not in non-carriers.