Abstract 1980: Identification of the transcription factor ZNF217 in ER+ subset of BC: A functional relationship with the PI3K-AKT-mTOR pathway
Authors: Dey Nandini , Williams Casey , Krie Amy , Solomon Ben , Starks David , Rojas Luis , Carlson Jennifer H. , Sun Yuliang , Lin Xiaoqian , Abramovitz Mark , Metzger-Nelson Timea , Williams Kirstin , Klein Jessica , De Pradip , Leyland-Jones Brian 
Published: August 2015

ZNF217 gene encodes for a Krüppel-like finger protein transcription factor. Here we report an amplification of ZNF217 gene in breast cancer (BC) patients. Retrospective study of 72 BC patients showed that ZNF217 gene was amplified in 12.5% of patients enrolled in our center over last ten months from February 2014 through November 2014. We found a similar level of amplification of ZNF217 gene at 20q13 in different epithelial cancers including lung, uterus, ovary, stomach, bladder and breast using data from c-Bioportal. The observed percentage of the amplification of ZNF217 gene in our patients (12.5%) was comparable to the c-BioPortal data which showed that this gene is altered (amplification, mutation, heterozygous deletion) in 12.1% (Breast Invasive Carcinoma; TCGA, Provisional; tumors with sequencing and CNA data; 962 samples) and in 13.3% (Breast Invasive Carcinoma; TCGA, Nature 2012; 825 samples) of all cases. In contrast to the cBioPortal data, we have observed only an amplification of ZNF217 gene in our patient samples. Amplification of ZNF217 gene was predominantly encountered in our ER+ patients (16.6%). Similarly 11% of the luminal A patients showed alterations in the ZNF217 gene while 24% of the luminal B showed alterations in the ZNF217 (Breast Invasive Carcinoma; TCGA, Nature 2012; 235 luminal A samples & 131 luminal B samples; cBioPortal). A comparable trend of higher mRNA expression (DASL analyses from FFPE; Dey et al. BMC Cancer 2013) for ZNF217 was also observed in the ER+/PR+/HER2+ tumor samples from our previously reported BC cohorts. The amplification of ZNF217 was validated by IHC expression in patient samples. The functional significance of ZNF217 in BC progression is not clear yet. In the cell line based models, Western blot data revealed the presence of this transcription factor in a number of BC cell lines including MCF7, MCF7-aro, MCF7-letrozole resistant, T-47D and BT-474. The function of ZNF217 was studied using ZNF217-SiRNA. SiRNA mediated downregulation of ZNF217 perturbed the metastasis-associated phenotypes including integrin-directed migration/invasion in a number of ER+ BC cells. The abrogation of migration was found to be associated with the inhibition of RAC1-GTPase activity. Better understanding of the mechanistic involvement of ZNF217 and its associated pathways may provide a novel target for future therapeutic intervention in breast carcinogenesis. The tumorigenic role of ZNF217 in the ER+ BC in the context of PIK3CA mutation and / or PTEN alterations is currently being worked out, the result of which will be presented at the meeting.

Citation Format: Nandini Dey, Casey Williams, Amy Krie, Ben Solomon, David Starks, Luis Rojas, Jennifer H. Carlson, Yuliang Sun, Xiaoqian Lin, Mark Abramovitz, Timea Metzger-Nelson, Kirstin Williams, Jessica Klein, Pradip De, Brian Leyland-Jones. Identification of the transcription factor ZNF217 in ER+ subset of BC: A functional relationship with the PI3K-AKT-mTOR pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1980. doi:10.1158/1538-7445.AM2015-1980