Recent studies have shown that chromatin-associated proteins and transcription factors have more somatic alterations than any other class of oncoproteins in childhood CNS tumors. Different Histone H3 genes (H3F3A, Hist3.1B) and variants (K27, G34, K36) can be affected with remarkable specific association between tumor location and type as well as the particular H3 residue or variant that is mutated. We have shown a high prevalence of H3 mutations in pediatric and young adult High Grade Astrocytoma, in sarcomas such as Giant Cell Tumors of the bone and chondroblastomas, and most recently, in Head and Neck Squamous Cell Carcinomas. These ground-breaking discoveries of oncohistones implicate a direct effect of epigenetic misregulation in oncogenesis. Here, we describe these epigenetic misfits and our knowledge of their effects, along with novel tools needed to study them. We will also discuss how we are harnessing synergies between the approaches of cancer genomics and chemical biology to help make sense of the pathogenesis of oncohistones and describe how oncohistones are promoting global redistribution of important epigenetic marks, seemingly hijacking our epigenome.

Citation Format: Nada Jabado. Oncohistones in cancer: How to turn a cell's symphony into non harmonic rap [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 PL04-04.