Abstract 4058: Race-associated breast cancer disparities: The role of CRYBB2 and its pseudogene

Abstract

Research demonstrates young African American (AA) women have higher mortality rates for triple-negative breast cancer (TNBC), despite lower incidence rates, when compared to Caucasian American (CA) women. These disparate poor patient outcomes may be attributed to access to quality care, socioeconomic status, education, or geographic location. However, numerous other studies have demonstrated that gene expression differences may also contribute to the higher mortality rates experienced by AA women, suggestive of biological differences among these two patient populations. Consequently, CRYBB2 is one gene that has consistently been associated with AA race in normal and malignant tissues. Although, its basic function in these tissues is currently unknown, higher expression of CRYBB2 is significantly correlated with poor outcome in breast, colorectal and prostate cancers in AAs. We analyzed all publically available gene expression datasets from studies focused on breast cancer health disparities and discovered that all probes detected CRYBB2 as well as its pseudogene, CRYBB2P1. It is becoming increasingly clear that pseudogenes have the ability to modify the mechanisms of their functional parental genes. However, it remains unclear whether the high expression of CRYBB2, CRYBB2P1, or both, affect cell behaviors to alter disease progression. Herein, we investigated the biological consequences of CRYBB2 and CRYBB2P1 in three basal-like TNBC cell lines (SUM159, MDA-MB-231, Hs578t) using CRISPR/Cas9 and overexpression technologies. The functional consequence of CRYBB2 and CRYBB2P1 expression were evaluated using in vitro and biochemical assays, as well as in vivo tumorigenesis studies. Our findings demonstrate overexpression of CRYBB2 and CRYBB2P1 alter cell proliferation, cytokine and growth factor production, and tumorigenesis. This data highlights the potential molecular mechanisms by which CRYBB2 and CRYBB2P1 contribute to poor patient outcome. Citation Format: Maya A. Barrow, Megan E. Martin, Denise K. Reaves, Breanna Jeffcoat, Ginger R. Smith, Michael Tarpley, Kevin P. Williams, Jodie M. Fleming. Race-associated breast cancer disparities: The role of CRYBB2 and its pseudogene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4058.