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

Crnobrnja, Bojana (author), Büdefeld, Tomaž (author), Glavač, Damjan (author), Jezernik, Gregor (author), Jurgec, Staša (author), Takač, Iztok (author), Potočnik, Uroš (author)

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 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.

• Language: English
• Keywords: GATA 3, somatic mutation, Slovenian population
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 14 str.
• Numbering: Vol. 10, iss. 4, art. 026140153
• PID: 20.500.12556/RUL-187353
• UDC: 618.19-006:577.21
• ISSN on article: 2587-196X
• DOI: 10.36922/EJMO026140153
• COBISS.SI-ID: 280428291
• Publication date in RUL: 10.09.2026

Record is a part of a journal

• Title: Eurasian journal of medicine and oncology
• Shortened title: Eurasian j. med. oncol.
• Publisher: AccScience
• ISSN: 2587-196X
• COBISS.SI-ID: 231016707

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• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.