Tamar Zahavi, Amir Sonnenblick, Yael Shimshon, Luna Kadouri, Tamar Peretz, Asher Y Salmon, Mali Salmon-Divon

About 5%-10% of breast cancer and 10%-15% of ovarian cancer are hereditary.BRCA1andBRCA2are the most common germline mutations found in both inherited breast and ovarian cancers. Once these mutations are identified and classified, a course of action to reduce the risk of developing either ovarian or breast cancer - including surveillance and surgery - is carried out. The purpose of the current research is to characterize the gene expression differences between healthy cells harboring a mutation inBRCA1/2 genes and normal cells. This will allow detection of candidate genes and help identify women who carry functionalBRCA1/2 mutations, which cannot always be detected by the available sequencing methods, for example, carriers of mutations found in regulatory sequences of the genes. Our cohort consisted of 50 healthy women, of whom 24 were individuals withBRCA1orBRCA2heterozygous mutations and 26 were non-carrier controls. RNA purified from non-irradiated lymphocytes of nineBRCA1/2 mutation carriers versus four control mutation-negative individuals was utilized for RNA-Seq analysis. The selected RNA-Seq transcripts were validated, and the levels of spleen tyrosine kinase (SYK) mRNA were measured by using real-time quantitative polymerase chain reaction. Differences in gene expression were found when comparing untreated lymphocytes ofBRCA1/2mutation carriers and controls. Among others, theSYKgene was identified as being differently expressed forBRCA1/2 mutation carriers. The expression level ofSYKwas significantly higher in untreated healthy lymphocytes ofBRCA1heterozygote carriers compared with controls, regardless of irradiation. In contrast to normal tissues, in cancerous breast tissues, the expression levels of theBRCA1andSYKgenes were not intercorrelated. Collectively, our observations demonstrate thatSYKmay prove to be a good candidate for better diagnosis, treatment, and prevention ofBRCA1mutation-associated breast cancer.