Abstract C47: microRNA expression profiling in normal breast epithelium of BRCA1 and BRCA2 carriers as prevention targets

Background: MicroRNAs (miRNA) are small, noncoding RNAs with important regulatory roles in tissue development, differentiation, proliferation, and when deregulated tumor formation. The goal of this study was to characterize the miRNA profile of normal breast tissue from carriers of either BRCA1 or BRCA2 mutations, with and without a prior history of cancer, for biomarker discovery for future prevention studies in high risk patient populations. Methods: MicroRNA profiling was conducted using a panel of breast candidate miRNAs and normal ‘non-cancerous’ tissue biopsy from 15 BRCA1 mutation carriers, 15 BRCA2 mutation carriers and 15 BRCA screened mutation negative subjects from high risk families. Results: While small differences were observed for any individual miRNA between groups, the most striking observation was the presence of a clear BRCA1 miRNA signature that was distinct from that in BRCA2 subjects or in the high-risk, non-mutation carriers. The BRCA1 pattern was present in normal appearing tissue biopsy independent of previous history of cancer, treatment for cancer, age, menopausal status or oophorectomy. BRCA2 carriers and high risk, mutation negative subjects showed an overall shared miRNA expression pattern. MicroRNA species that distinguished the groups included differences in the expressed levels of let-7a, let-7b, miR-125b, miR-145, miR-15b and members of the miR-181 family. Ongoing efforts include pathway modeling to gain insight on novel targets for prevention along with RT-PCR confirmation of differentiating microRNA species as well the potential downstream targets for example of miR-181b target genes including HOXA7, HOXA9, HOXA11 and PBX3. Conclusion: The presence of a distinctive miRNA profile in normal appearing tissue of BRCA1 mutation carriers suggest a major role of BRCA1 mutation status on the normal tissue not previously reported. If corroborated, miRNA profiling studies of normal breast tissue may prove useful in both risk assessment as well as providing insight on deregulated pathways for pharmacologic intervention for risk reduction in the BRCA carrier population. Citation Format: Sandhya Pruthi, Julie Buckmeier, Christina Preese, Vera J. Suman, Rachel M. Hurley, Patricia Thompson. microRNA expression profiling in normal breast epithelium of BRCA1 and BRCA2 carriers as prevention targets. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C47.