Serbian high-risk families: Extensive results on BRCA mutation spectra and frequency

Abstract

Mutations in BRCA genes elevate risk for breast and ovarian cancer. These mutations are population specific. As there are no data on BRCA mutation screening on larger number of probands in Serbia to date, aim of this study was to determine types and frequencies of BRCA mutations in individuals from high-risk families from Serbia, as well as to determine which BRCA mutations may be considered as founder for Serbian population. We analyzed 94 probands and detected 9 frameshift mutations in 12 individuals, 1 benign BRCA2 nonsense mutation and numerous missense and synonymous mutations in both genes. Frequency of frameshift mutations is 12.77%. In addition to two novel mutations detected in our population we reported previously, we detected another novel mutation - c.7283delT in BRCA2 exon 14. None of the detected deleterious mutations may be considered as founder mutations for Serbian population, as each of them was found in no more than two high-risk families. This mutation diversity is most probably due to high migration rate in history of this part of Europe. Interpretation of genetic testing results with missense mutations of unknown clinical importance is very challenging and should be approached with caution, using all available data sources for results' interpretation.