expression level distinguishes control from -mutated lymphocytes.

BACKGROUND

About 5%-10% of breast cancer and 10%-15% of ovarian cancer are hereditary. and are 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.

PURPOSE

The purpose of the current research is to characterize the gene expression differences between healthy cells harboring a mutation in /2 genes and normal cells. This will allow detection of candidate genes and help identify women who carry functional /2 mutations, which cannot always be detected by the available sequencing methods, for example, carriers of mutations found in regulatory sequences of the genes.

MATERIALS AND METHODS

Our cohort consisted of 50 healthy women, of whom 24 were individuals with or heterozygous mutations and 26 were non-carrier controls. RNA purified from non-irradiated lymphocytes of nine /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 () mRNA were measured by using real-time quantitative polymerase chain reaction.

RESULTS

Differences in gene expression were found when comparing untreated lymphocytes of mutation carriers and controls. Among others, the gene was identified as being differently expressed for /2 mutation carriers. The expression level of was significantly higher in untreated healthy lymphocytes of heterozygote carriers compared with controls, regardless of irradiation. In contrast to normal tissues, in cancerous breast tissues, the expression levels of the and genes were not intercorrelated.

CONCLUSION

Collectively, our observations demonstrate that may prove to be a good candidate for better diagnosis, treatment, and prevention of mutation-associated breast cancer.