Abstract B10: Genome-wide analysis of p53 transcriptional programs in Myc-induced lymphomas

Abstract

Abstract Oncogenic activation of Myc induces cellular transformation and hyper-proliferation, while it activates intrinsic tumor surveillance pathways aimed at restraining the expansion of pre-cancerous cells. All these Myc-induced tumor suppressive mechanisms converge on p53, and loss of p53 activity is the major selected event in lymphomagenesis. Yet, the genetic programs triggered by p53 in tumor suppression have been only partially clarified. Using whole genome mapping of p53 binding and gene expression profiling, we investigated the transcriptional circuitry employed by p53 in suppressing cancer development. We studied the progression of Myc-induced lymphomas in Eµ-myc transgenic mice, as well as the regression of these lymphomas following restoration of p53 function, by either pharmacological or genetic means. We thus identified a set of p53 target genes that are strong candidates for mediating tumor suppression. Currently, we are testing the impact of these new components of the p53 transcriptional program on tumorigenesis with an RNA interference (RNAi)-based functional genetic screen. Altogether our data expand our understanding of the p53 response to Myc-induced oncogenic stress and will hopefully highlight new tumor suppressive mechanisms, paving the way for their therapeutic application. Citation Format: Claudia Tonelli, Marco J. Morelli, Arianna Sabò, Andrea Piontini, Mattia Pelizzola, Stefano Campaner, Bruno Amati. Genome-wide analysis of p53 transcriptional programs in Myc-induced lymphomas. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B10.