AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO026140153
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ORIGINAL RESEARCH ARTICLE

Characterization of GATA3 mutational status in early-stage breast cancer patients from Slovenia

Bojana Crnobrnja1 ,  Tomaž Büdefeld2 ,  Damjan Glavač2,3 ,  Gregor Jezernik2,4 ,  Staša Jurgec2,5 ,  Iztok Takač1† ,  Uroš Potočnik2,4,6†*
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1 Division of Gynecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia
2 Centre for Human Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia
3 Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
4 National-Level Institute for Sustainable Environmental Solutions, Maribor, Slovenia
5 Laboratory for Biochemistry, Molecular Biology and Genomics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia
6 Department for Science and Research, University Medical Centre Maribor, Maribor, Slovenia
†These authors contributed equally to this work.
EJMO, 026140153 https://doi.org/10.36922/EJMO026140153
Received: 31 March 2026 | Revised: 23 April 2026 | Accepted: 6 May 2026 | Published online: 3 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: 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 ERα 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.

Keywords
Breast cancer
GATA3
Somatic mutation
Immunohistochemistry
Slovenian population
Funding
This research was funded by the Slovenian Research and Innovation Agency through research core funding (Nos. P3-0427, P3-0067, P3-0321, and I0-0029) and research grants Nos. J3-9272 and J3-3069; the University Medical Centre Maribor internal grants (Nos. IRP-2019/01-05 and IRP-2019/02-15); and the Republic of Slovenia, the Ministry of Higher Education, Science and Innovation, and the European Union from the European Regional Development Fund under grant RIUM.
Conflict of interest
The authors declare they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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