2026-04-29T04:10:24Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/181892024-11-29T15:47:54Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Hruschka, Natascha author Kalisz, Mark author Subijana, Maria author Graña-Castro, Osvaldo author Del Cano-Ochoa, Francisco author Brunet, Laia Paré author Chernukhin, Igor author Sagrera, Ana author De Reynies, Aurelien author Kloesch, Bernhard author Chin, Suet-Feung author Burgués, Octavio author Andreu, David author Bermejo, Begoña author Cejalvo, Juan Miguel author Sutton, Joe author Caldas, Carlos author Ramón-Maiques, Santiago author Carroll, Jason S author Prat, Aleix author Real Arribas, Francisco author Martinelli, Paola author 2020-08 As the catalog of oncogenic driver mutations is expanding, it becomes clear that alterations in a given gene might have different functions and should not be lumped into one class. The transcription factor GATA3 is a paradigm of this. We investigated the functions of the most common GATA3 mutation (X308_Splice) and five additional mutations, which converge into a neoprotein that we called "neoGATA3," associated with excellent prognosis in patients. Analysis of available molecular data from >3000 breast cancer patients revealed a dysregulation of the ER-dependent transcriptional response in tumors carrying neoGATA3-generating mutations. Mechanistic studies in vitro showed that neoGATA3 interferes with the transcriptional programs controlled by estrogen and progesterone receptors, without fully abrogating them. ChIP-Seq analysis indicated that ER binding is reduced in neoGATA3-expressing cells, especially at distal regions, suggesting that neoGATA3 interferes with the fine tuning of ER-dependent gene expression. This has opposite outputs in distinct hormonal context, having pro- or anti-proliferative effects, depending on the estrogen/progesterone ratio. Our data call for functional analyses of putative cancer drivers to guide clinical application. Oncogene . 2020;39(32):5455-5467. http://hdl.handle.net/20.500.12105/18189 32587399 10.1038/s41388-020-1376-3 1476-5594 Oncogene https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410826/ The GATA3 X308_Splice breast cancer mutation is a hormone context-dependent oncogenic driver.