In addition, a subset of <i>Rb1/Trp53/Crebbp</i>-deficient SCLC exhibited exceptional responses to Pracinostat <i>in vivo</i> Thus, CREBBP acts as a potent tumor suppressor in SCLC, and inactivation of CREBBP enhances responses to a targeted therapy.<b>Significance:</b> Our findings demonstrate that CREBBP loss in SCLC reduces histone acetylation and transcription of cellular adhesion genes, while driving tumorigenesis.
While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations.