Functional Impact of Chromatin Remodeling Gene Mutations and Predictive Signature for Therapeutic Response in Bladder Cancer.

ABSTRACT: Urothelial carcinoma accounts for most of the bladder cancer cases. Using next-generation sequencing (NGS) technology, we found that a significant percentage (83%) of tumors had mutations in chromatin-remodeling genes. Here, we examined the functional relevance of mutations in two chromatin-remodeling genes, EP300 and its paralog, CREBBP, which are mutated in almost one-third of patients. Interestingly, almost half of missense mutations cluster in the histone-acetyltransferase (HAT) domain of EP300/CREBBP. This domain catalyzes the transfer of an acetyl group to target molecules such as histones, thereby regulating chromatin dynamics. Thus, patients with EP300 or CREBBP mutations may have alterations in the ability of the corresponding proteins to modify histone proteins and control transc

SUBMITTER: Duex JE 

PROVIDER: S-EPMC5951683 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature