Article
Selective Inhibition of HDAC3 Targets Synthetic Vulnerabilities and Activates Immune Surveillance in Lymphoma.
Cancer discovery - 1 Mar 2020
Mondello Patrizia, Tadros Saber, Teater Matt, Fontan Lorena, Chang Aaron Y, Jain Neeraj, Yang Haopeng, Singh Shailbala, Ying Hsia-Yuan, Chu Chi-Shuen, Ma Man Chun John, Toska Eneda, Alig Stefan, Durant Matthew, de Stanchina Elisa, Ghosh Sreejoyee, Mottok Anja, Nastoupil Loretta, Neelapu Sattva S, Weigert Oliver, Inghirami Giorgio, Baselga José, Younes Anas, Yee Cassian, Dogan Ahmet, Scheinberg David A, Roeder Robert G, Melnick Ari M, Green Michael R
Abstract excerpt
CREBBP mutations are highly recurrent in B-cell lymphomas and either inactivate its histone acetyltransferase (HAT) domain or truncate the protein. Herein, we show that these two classes of mutations yield different degrees of disruption of the epigenome, with HAT mutations being more severe and associated with inferior clinical outcome. Genes perturbed by CREBBP mutation are direct targets of the BCL6-HDAC3...
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