Abstract 3936: Bromodomain testis-specific protein BRDT is expressed in a subset of esophageal squamous cell carcinomas and controls expression of differentiation-associated genes

Abstract

Abstract Esophageal cancer is one of the most malignant cancers, ranking as the sixth leading cause of cancer-related deaths worldwide. The poor survival rate and prognosis highlight the limitations in the biological understanding of esophageal cancer and the urgent need for identification of novel targeted molecular therapies. Recently, large scale genomic analyses have revealed the extensive alternations of epigenetic regulators which may be used as a basis for developing new “epigenetic drugs “. BRDT, bromodomain testis-specific protein, is a member of the bromodomain and extra-terminal (BET) family of epigenetic reader proteins. BET proteins can regulate gene expression by recognizing acetylated lysines, thus playing important roles in both normal development and disease progression. Inhibition of BET proteins has emerged as a potential therapy for many types of cancer. In normal human tissues, unlike the other members of BET family, BRDT is exclusively highly expressed in testes where it drives the meiotic and post-meiotic gene expression to promote spermatogenesis. We have identified BRDT to be expressed in over 20% of esophageal squamous cell carcinoma (ESCC), a predominant subtype of esophageal cancer. Knockdown of BRDT does not affect cell proliferation, but leads to alterations in the expression of differentiation markers. In addition, RNA-seq following BRDT knockdown also supports a role of BRDT in cell differentiation. Depletion of BRDT does not alter the cellular response to BET inhibition. Surprisingly, we also identified BRDT transcripts encoding two truncated isoforms lacking the first bromodomain, which could potentially alter its epigenetic reader function. The genome occupancy profile of BRDT showed a significant enrichment at transcription start site (TSS), which is distinct from BRD4. It also showed potential interactions between BRDT and E2F family and SMAD family. Together, we showed that BRDT is overexpressed in ESCC cell lines and may influence ESCC development or progression in a subset of tumors by regulating cell differentiation-associated genes. Citation Format: Xin Wang, Feda H. Hamdan, Madhobi Sen, Ana P. Kutschat, Steven A. Johnsen. Bromodomain testis-specific protein BRDT is expressed in a subset of esophageal squamous cell carcinomas and controls expression of differentiation-associated genes [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 3936.