A class of GATA3 mutation reprograms the breast cancer transcriptional network through gain and loss of function

Dr. Paul Wade, Motoki Takaku, Dr. Sara Grimm, John Roberts, Kaliopi Chrysovergis, Dr. Brian Bennett, Page Myers, Lalith Perera, Dr. Charles Perou

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Received: 13th October 17

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.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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