Abstract 1192: ZMIZ1 is elevated in epithelial ovarian cancer due to an upregulated alternative promoter and is associated with p53 mutations

Abstract

Abstract Objectives: The ZMIZ1 gene has recently been found to be a possible, candidate oncogene through a transposon mutagenesis screen. It is widely known that one of the most common genetic alterations in epithelial ovarian cancer involves mutations of the p53 tumor suppressor gene. Previous studies have shown that ZMIZ1 appears to transcriptionally regulate the p53 gene. We hypothesize that ZMIZ1 expression is caused by the presence of an alternative promoter and that the interaction between ZMIZ1 and p53 may impart worse survival. Methods: A retrospective chart review was performed to identify 138 patients with epithelial ovarian cancer. Data collected included clinico-pathologic factors, patient follow-up, and mortality. ZMIZ1 staining and p53 sequencing were performed on all patients. For the determination of ZMIZ1 alternative promoter relative gene expression, RT-PCR was performed on 33 tumors after cDNA had been isolated. Statistical analyses included chi-square analysis and the binomial test. The log rank test was used to evaluate survival analysis. Results: Immunostaining for the ZMIZ1 protein was performed with the following results: 55 (40%) tumors stained positive and 83 (60%) were negative. Of those patients that were found to be ZMIZ1 positive, over half were noted to have a p53 gene mutation. The median survival of the ZMIZ1 positive/p53 mutated cohort was approximately 36 months while the median survival for the ZMIZ1 negative/p53 wild type cohort was 84 months (p = 0.012). ZMIZ1 alternative promoter relative gene expression was noted to be elevated in patients with ZMIZ1 positive immunostaining compared to patients with negative staining. Conclusions: ZMIZ1 staining appears to be present in 40% of patients with epithelial ovarian cancer. In tumors that are ZMIZ1 positive, half contain p53 gene mutations; this combination imparts worse survival. ZMIZ1 upregulation may be due to the presence of a newly identified alternative promoter. Additional studies are ongoing to better define the role of this alternative promoter. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1192. doi:1538-7445.AM2012-1192