Abstract P2-05-14: The long noncoding RNA BHLHE40-AS1 as a functional biomarker of invasive breast cancer

Increased emphasis on breast cancer screening has led to a dramatic surge in diagnosis of pre-cancerous ductal carcinoma in situ (DCIS) over the past 30 years. Unfortunately, diagnosis of late stage invasive and metastatic disease has not proportionally declined, suggesting significant over diagnosis and over treatment of innocuous DCIS. Due to a lack of biomarkers, the heterogeneity of DCIS lesions, and an insufficient understanding of mechanisms of invasive progression, there is currently no clinically relevant method of predicting which DCIS lesions will advance to invasive disease. As a result, all DCIS patients undergo an aggressive treatment regimen to prevent disease progression. Therefore, there is a critical need to determine the underlying mechanisms driving breast cancer progression to better inform patient treatment options and nominate novel therapeutic entry points for treatment of invasive disease. Recently, long noncoding RNAs (lncRNAs) have gained attention as critical regulators of epigenetic states and gene expression. Although the study of lncRNAs is in its infancy, they are being uncovered as pivotal regulators of development and tumorigenesis, thus they are a rich source of potential drivers of breast cancer progression. We propose that lncRNAs functionally drive breast cancer invasion and their expression can discriminate between innocuous and potentially invasive DCIS. Using biopsies from women that exhibit tandem DCIS and invasive breast cancer lesions, we have identified a cohort of long noncoding RNAs (lncRNAs) that are enriched in the invasive biopsy. From this cohort we have identified the lncRNA BHLHE40-AS1 as increasing in a step-wise manner in a breast cancer progression series that escalates from normal, non-transformed cells to highly invasive disease. Preliminary evidence suggests that BHLHE40-AS1 expression regulates invasive potential in vitro. Using a GeneChip® Human Transcriptome 2.0 Array (HTA) we have identified several targets previously associated with driving breast cancer invasion as being potentially regulated by BHLHE40-AS1. Future directions will focus on determining the effect of BHLHE40-AS1 expression on tumor cell invasion in an orthotopic xenograft model, mechanistically elaborating its function, and determining the utility of BHLHE40-AS1 as a clinically relevant biomarker of invasive breast cancer. Citation Format: DeVaux RKS, Davis S, Sheftel J, Coarfa C, Behbod F, Herschkowitz JI. The long noncoding RNA BHLHE40-AS1 as a functional biomarker of invasive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-14.