Characterization of GATA3 mutational status in early-stage breast cancer patients from SloveniaCrnobrnja, Bojana (Avtor) Büdefeld, Tomaž (Avtor) Glavač, Damjan (Avtor) Jezernik, Gregor (Avtor) Jurgec, Staša (Avtor) Takač, Iztok (Avtor) Potočnik, Uroš (Avtor) GATA 3somatic mutationSlovenian populationIntroduction: GATA3 is a zinc-finger transcription factor essential for luminal cell fate specification in the mammary gland and a well-established marker of estrogen receptor (ER)-positive breast cancer (BC). High GATA3 expression characterizes the luminal A subtype and is associated with a favorable prognosis, while reduced expression and somatic mutations in its zinc-finger and C-terminal domains have been linked to aggressive tumor behavior. However, the molecular determinants of GATA3 loss in early-stage BC remain poorly understood. Objective: To characterize GATA3 mutational status in early-stage breast cancer patients. Methods: We characterized GATA3 protein expression by immunohistochemistry and assessed somatic mutations in exons 2–6 in a prospective cohort of 60 early-stage BC patients from Slovenia. We additionally performed a comprehensive analysis of somatic variations across the GATA3 gene using COSMIC data and evaluated the structural impact of single-nucleotide variants (SNVs) on GATA3 protein stability using in silico tools. Results: Most tumors (90%) exhibited high GATA3 immunoreactivity, which correlated significantly with with ER$\alpha$ expression (p = 0.006). No somatic mutations were identified in exons 2–6 in tumors with absent or low GATA3 expression, suggesting that epigenetic mechanisms such as promoter hypermethylation drive expression loss in early-stage disease. Among 469 COSMIC-cataloged somatic variations, frameshift mutations predominated, and exon 6 harbored the highest mutational burden (55.88%). In silico analysis revealed that 51.46% of SNVs exerted destabilizing effects on GATA3 structure, predominantly within the zinc-finger 2 domain. Two variants, P42L and S93F, exhibited stabilizing effects warranting further functional investigation. Conclusion: Our findings provide characterization of GATA3 in early-stage BC from Slovenia and implicate epigenetic silencing as an alternative mechanism of GATA3 inactivation.20262026-09-10 11:06:06Članek v reviji187353sl