Abstract 2090: The GNAQ T96S mutation enhances the oncogenic properties of breast cancer

Abstract Breast cancer (BC) is the most commonly diagnosed cancer in the world, and metastatic breast cancer (mBC) remains responsible for the majority of breast cancer deaths. In this study, we collected 615 cases of Taiwanese BC patient's tumor samples and used whole exome sequencing (WES) to clarify the genetic mutation landscape of this population. We have compared with various BC genomic databases such as TCGA, COSMIC, and MSKCC to identify 29 novel variants in 18 genes that were predicted to have a pathogenic effect. In these pathogenic variants, we found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was presented in 116 out of 615 BC patients (18. 9%). To examine the effect of the GNAQ T96S mutation on BC, we transfected the MCF-7 and MDA-MB-231 cell lines with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the GNAQ T96S expression vector enhanced cell proliferation, colony formation, migration, and activation of the MAPK pathways compared to wild-type GNAQ expression MCF-7 cells. We also found that the tumorigenicity, and tumor growth were significantly increased in the GNAQ T96S expressed MCF-7 xenograft model, and exhibited higher rates of lung metastasis in GNAQ T96S expressed MDA-MB-231 cells. Our data suggest that the GNAQ T96S mutation may play an oncogenic role in BC by potentiating the GNAQ signaling pathway. In this study, we also found several compounds that can inhibit in vitro cell proliferation and in vivo tumor growth of GNAQ T96S expressed MCF-7 cells. These compounds showed the potential to treat the mBC patients who have GNAQ T96S mutation. Citation Format: Ming-Hsi Wu, Hsiang-Ching Wang, Wei-Hsin Wang, Yen-Ju Lin, Wan-Ru Chen, Shih-Ta Chen, Chih-Wei Fu, Eric Chuang. The GNAQ T96S mutation enhances the oncogenic properties of breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2090.