Abstract
RAD51D gene’s protein product is known to be involved in the DNA repair mechanism by homologous recombination. RAD51D germline mutations have been recently associated with ovarian and breast cancer (OC and BC, respectively) predisposition. Our aim was to evaluate the frequency of hereditary RAD51D mutations in Greek patients. To address this, we have screened for RAD51D germline mutations 609 BRCA1- and BRCA2-negative patients diagnosed with OC, unselected for age or family history, and 569 BC patients diagnosed under 55 years and with an additional relative with BC or OC. We identified four pathogenic mutations in four unrelated individuals with family history of BC and/or OC. Three of the RAD51D carriers had developed BC, while the other one was an OC patient, thus accounting for a mutation frequency of 0.16% in the OC cohort and 0.53% in the BC cohort. One of the detected mutations is novel (c.738 + 1G > A), whereas the rest had been detected previously (p.Gln151Ter, p.Arg186Ter, and p.Arg300Ter). It is noteworthy that the 4 carrier families had 13 BC cases and only 4 OC cases. Our data support that RAD51D should be implemented into the comprehensive multigene panel, as mutation carriers may benefit from the administration of PARP inhibitors.
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We thank the patients and their families for their participation in this study.
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Konstanta, I., Fostira, F., Apostolou, P. et al. Contribution of RAD51D germline mutations in breast and ovarian cancer in Greece. J Hum Genet 63, 1149–1158 (2018). https://doi.org/10.1038/s10038-018-0498-8
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DOI: https://doi.org/10.1038/s10038-018-0498-8
