Abstract 4782: Genome-wide chromatin profiling in bladder and prostate cancers

Mutations in a few driver genes can cause cancer, and a main goal of cancer genome analysis has been the identification of these cancer genes. Recent findings, however, indicate that deregulation of enhancers can play a major role in carcinogenesis. In this study, we aim to understand how enhancer networks evolve during cancer initiation and progression and to identify epigenetic states that are predictive of cancer stage and drug response. We surveyed 15 bladder cell lines, including the T24 lineage (T24, T24T, FL, and SL) and the UMUC3 lineage (UMUC3 and LUL2), and 10 prostate cancer cell lines including BPH1, DU145 and LNCap. These cell lines display different tumorigenic and metastatic potentials, and thus present a model for cancer progression and development of castration-resistance. DNase-seq was performed to map genome-wide regulatory profiles in these cells. The enhancers detected as DNase I hypersensitivity sites (DHSs) showed large-scale changes in the chromatin accessibility landscape during the acquisition of tumorigenic and metastatic phenotypes. Selective sets of gained or lost DHSs were identified. Among the changes during the T24 to T24T transition, the loss of DHSs was remarkable. Some of these DHSs were found near genes that are in the downstream response to HDACs. Induction of expression by the HDAC inhibitor, Na butyrate, was correlated with DNase-seq signal for these genes. Gene Ontology (GO) enrichment analysis also indentified a set of genes neighboring lost DHSs that belong to the focal adhesion class in GO category. This study identified a set of DHSs that were associated with cancer progression in bladder and prostate cancer, and the potential clinical application of the identified DHSs will be discussed. Citation Format: Sohyoung Kim, Lyuba Varticovski, Qizong Lao, Songjoon Baek, Myong-Hee Sung, Lars Grontved, Michael L. Nickerson, Bethtrice Thompson, Dan Theodorescu, Michael Dean, Gordon H. Hager. Genome-wide chromatin profiling in bladder and prostate cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4782. doi:10.1158/1538-7445.AM2015-4782