Abstract P5-18-10: BHLHE40-AS1 is an enhancer associated long noncoding RNA critical to breast cancer progression

Abstract

Abstract Increased emphasis on breast cancer screening has led to a dramatic increase in diagnosis of ductal carcinoma in situ (DCIS). DCIS lesions are nonobligate precursors of invasive ductal carcinoma (IDC) and thus, the current standard-of-care is aggressive therapy to prevent invasive and metastatic disease. However, only ˜40% of DCIS cases are predicted to progress leading to a current state of overtreatment and overdiagnosis. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive breast cancers and refine patient treatment strategies.We propose that long noncoding RNAs (lncRNAs) functionally drive breast cancer progression and their expression can discriminate between innocuous and potentially invasive DCIS. Using biopsies from women with tandem DCIS and IDC lesions, we identified 35 lncRNAs whose expression can distinguish between pre-invasive and invasive disease. From this candidate list, the lncRNA BHLHE40-AS1 is found enriched in multiple breast cancer progression models, in HER2+ cell lines, and HER2+ patient tumors. Functionally, BHLHE40-AS1 is found to support tumor cell cycle and motility and may serve as a clinically relevant biomarker and therapeutic target in invasive breast cancer. Further, BHLHE40-AS1 is expressed from a known super-enhancer that preliminary evidence suggests undergoes altered chromatin looping during breast cancer progression. Interestingly, over half of the candidate lncRNAs are associated with enhancer regions. Current studies are investigating super-enhancers, and associated lncRNAs that become acquired during breast cancer progression. Citation Format: DeVaux RS, Schimjawicz H, Coarfa C, Behbod F, Herschkowitz JI. BHLHE40-AS1 is an enhancer associated long noncoding RNA critical to breast cancer progression [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-10.