A growing emphasis in anticancer drug discovery efforts has been on targeting histone acetylation modulators. Here we comprehensively analyze the genomic alterations of the genes encoding histone acetylation modulator proteins (HAMPs) in the Cancer Genome Atlas cohort and observe that HAMPs have a high frequency of focal copy number alterations and recurrent mutations, whereas transcript fusions of HAMPs are relatively rare genomic events in common adult cancers. Collectively, 86.3% (63/73) of HAMPs have recurrent alterations in at least 1 cancer type and 16 HAMPs, including 9 understudied HAMPs, are identified as putative therapeutic targets across multiple cancer types. For example, the recurrent focal amplification of BRD9 is observed in 9 cancer types and genetic depletion of BRD9 inhibits tumor growth. Our systematic genomic analysis of HAMPs across a large-scale cancer specimen cohort may facilitate the identification and prioritization of potential drug targets and selection of suitable patients for precision treatment.

Highlights d Recurrent genomic alterations of the genes encoding CDKs/ cyclins are characterized d CDKs/cyclins are dominantly driven by copy-number aberrations across cancers d CDK7 losses are correlated with increased sensitivities to DNA-damaging drugs d Low-dose CDK7i treatment sensitizes HR-proficient cancer cells to PARPi

The development of effective receptor-targeted nonviral vectors for use in vivo is complicated by a number of technical problems. One of these is the low efficiency of the conjugation procedures used to couple protein ligands to the DNA condensing carrier molecules. We have made and characterized a multi-domain protein (SPKR) 4 inv, that is designed to target plasmid DNA to ␤ 1 integrins in remodeling tissue. It contains a nonspecific DNA-binding domain (SPKR) 4 , a rigid ␣-helical linker, and the C-terminal ␤ 1 integrin binding domain (aa 793-987) of the Yersinia pseudotuberculosis invasin protein. (SPKR) 4 inv could be purified at high yields using a bacterial expression system. We show that (SPKR) 4 inv binds with high affinity to both plasmid DNA and ␤ 1 integrins. In a cell attachment assay, the apparent affinity of (SPKR) 4 inv for ␤ 1 integrins is three orders of magnitude