Abstract 2992: Transcriptional silencing of amplicons by histone deacetylase inhibition

Inhibition of cancer cell growth by histone deacetylase (HDAC) inhibitors has been observed in a number of malignancies. Multiple mechanisms have been proposed to explain the cancer-specific cytotoxic effect of HDAC inhibition, including transcriptional activation of pro-apoptotic and differentiation programs that become epigenetically silenced during tumorigenesis. Here, we report a direct transcriptional repression mechanism of histone deacetylase inhibition that selectively targets genomic amplicons, providing genetic and epigenetic alterations as a basis for the cancer selective cytotoxicity of these drugs. Our study implicates distinct epigenetic structures at the oncogenic amplicons that might be targeted for cancer drug development. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2992.