title: Amplification of the bromodomain-containing protein 4 gene in ovarian high-grade serous carcinoma is associated with worse prognosis and survival.
abstract: High-grade serous carcinoma (HGSC) of the ovary is an aggressive and devastating neoplasm and the identification of novel therapeutic targets may result in a significant decrease in patient morbidity and mortality. Over the last few years, chromatin regulators have become attractive targets for cancer therapy. More specifically, bromodomain-containing protein 4 (BRD4), a protein that is associated with acetylated chromatin and transcriptional activation, has been shown to selectively regulate the transcription of key oncogenic drivers, such asCMYC, in several tumor types. The Cancer Genome Atlas (TCGA) Project has molecularly characterized the genome of ovarian serous carcinomas, which enabled us to study the association of genomic alterations ofBRD4with patient survival and clinicopathological characteristics. Our analysis using clinical and genomic data from the TCGA ovarian carcinoma samples revealed that somatic amplification ofBRD4(observed in 12% of the cases) was correlated with increasedBRD4mRNA levels and is significantly associated with worse overall and progression-free survival compared to wild-type cases. These findings support the hypothesis that future studies and trials investigating newly developed BRD4 inhibitors are required in a subset of patients with ovarian HGSC.
authors.affiliation: The Jackson Laboratory For Genomic Medicine, Farmington, CT 06030, USA.
authors.forename: Duygu
authors.initials: D
authors.lastname: Ucar
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Douglas I
authors.initials: DI
authors.lastname: Lin
keywords: MYC; The Cancer Genome Atlas project; bromodomain-containing protein 4; ovarian cancer; serous carcinoma