Jórunn Erla Eyfjörd did her undergraduate studies at the University of Iceland and University of Minnesota and her doctoral studies on DNA repair of radiation damage at the MRC Cell Mutation Unit, University of Sussex, England. She has led research on cancer genetics for many years, first at the Icelandic Cancer Society and later as Professor of genetics at the Faculty of medicine, University of Iceland. Jórunn participated in the search for breast cancer susceptibility genes and found with her collaborators a local founder mutation, 999del5, in the BRCA2 gene in 1996. She has studied the population impact of mutations in the BRCA1 and BRCA2 genes in Iceland and their clinical importance in breast and prostate cancer. She has also worked on epigenetics, BRCA-ness, telomere maintenance and genomic instability, as well as BRCA targeted cancer treatment. Jórunn has participated in many international collaborations, including most recently, the International Cancer Genome Consortium.
Abstract of the plenary talk
Title: Genomic instability and cancer
Affiliation: Jórunn Erla Eyfjörd, Faculty of Medicine University of Iceland
Mutations and complex genomic rearrangements characterize most human cancer cells. Inherited mutations in the BRCA1 and BRCA2 genes confer significantly increased risk of breast, ovarian and other cancers. Soon after the discovery of these genes there were indications that their protein products could be involved in repair of DNA damage. We discovered an Icelandic BRCA2 founder mutation, 999del5, that was strongly associated with chromosomal instability in breast tumors, suggesting a possible defect in the repair of DNA double strand breaks. Analyses of BRCA2 999del5 breast tumors and cell lines also showed end-to-end chromosome fusions and rearrangements, suggesting deficiency in telomere maintenance. Detailed analyses of breast tissue sections from BRCA mutation carriers and non-carriers, using Fluorescence in Situ Hybridization method (Q-FISH), show a clear difference in telomere length between different cell types, with the inner epithelial cells in the breast duct having shorter telomeres than both myoepithelial cells and fibroblasts. Most breast cancers are known to originate in the inner breast epithelium.
Further studies, using different types of microarrays, showed that both BRCA1 and BRCA2 defective tumors are characterized by specific genomic instability and interestingly, that loss of the wild type allele in tumors was associated with worse prognosis. In addition, BRCA-like patterns were seen in a subset of non-mutated tumors. Whole Genome Sequencing of breast tumor samples confirms our findings and those of others that a sizable part of breast cancers (larger than the BRCA mutation carriers alone) can be defined as BRCA-like, i.e. showing defects in homologous recombination repair (HR) of DNA double strand breaks. BRCA-targeted treatment, using PARP inhibitors, is a promising option for treatment of BRCA1 and BRCA2 deficient breast, ovarian, pancreatic and prostate cancer, and potentially also for the larger group of such cases with HR deficiency.