PT - JOURNAL ARTICLE AU - Motoki Takaku AU - Sara A. Grimm AU - John D. Roberts AU - Kaliopi Chrysovergis AU - Brian D. Bennett AU - Page Myers AU - Lalith Perera AU - Charles J. Tucker AU - Charles M. Perou AU - Paul A. Wade TI - A class of GATA3 mutation reprograms the breast cancer transcriptional network through gain and loss of function AID - 10.1101/204289 DP - 2017 Jan 01 TA - bioRxiv PG - 204289 4099 - http://biorxiv.org/content/early/2017/10/16/204289.short 4100 - http://biorxiv.org/content/early/2017/10/16/204289.full AB - GATA3 is frequently mutated in breast cancer; these mutations are widely presumed to be loss of function. Here, we address molecular alterations downstream of a novel class of GATA3 mutations, revealing both gain and loss of function. Mutation of one allele of GATA3 led to loss of binding and decreased expression at a subset of genes, including Progesterone Receptor. At other loci, associated with epithelial to mesenchymal transition, gain of binding at a novel sequence motif correlated with increased gene expression. These results demonstrate that not all GATA3 mutations are equivalent and that these mutations impact breast cancer through gain and loss of function.