Abstract IA20: Genomics of a STAT1 knockout mouse model of human ER+ breast cancer

Abstracts: AACR Special Conference: Advances in Breast Cancer; October 17-20, 2015; Bellevue, WA Estrogen receptor alpha positive luminal breast cancers are the most frequent subtype of breast cancer. Previous work has established that Stat1-/- mouse mammary tumor model recapitulates signaling, expression and phenotypic alterations observed in this subtype of human breast cancers. To identify transforming events that contribute to tumorigenesis, we performed whole genome sequencing of 22 Stat1-/- primary mammary tumors and cell lines. We discovered a novel hotspot of somatic mutations in 100% of tumors that resulted in a truncated form of the prolactin receptor (Prlr). Targeted sequence analysis identified similar mutations in 77.8% of ductal carcinoma in situ. Co-expression of truncated and full-length Prlr in normal cells led to activation of oncogenic Stat3 and Stat5 as well as cellular transformation. In conclusion, truncating mutations of Prlr drive tumor development in a model of human ERa+ breast cancer and should be considered as novel antitumor targets. Citation Format: Elaine Mardis, Obi L. Griffith, Ruby Chan Szeman, Malachi Griffith, Kilannin Krysiak, Zachary Skidmore, Jasreet Hundal, Julie A. Allen, Arthur Cora, Alexander P. Miceli, Heather Schmidt, Lee Trani, Krishna-Latha Kanchi, Christopher A. Miller, David E. Larson, Robert S. Fulton, Richard K. Wilson, Robert D. Schreiber. Genomics of a STAT1 knockout mouse model of human ER+ breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr IA20.