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

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

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.

• Jezik: Angleški jezik
• Ključne besede: GATA 3, somatic mutation, Slovenian population
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 14 str.
• Številčenje: Vol. 10, iss. 4, art. 026140153
• PID: 20.500.12556/RUL-187353
• UDK: 618.19-006:577.21
• ISSN pri članku: 2587-196X
• DOI: 10.36922/EJMO026140153
• COBISS.SI-ID: 280428291
• Datum objave v RUL: 10.09.2026

Gradivo je del revije

• Naslov: Eurasian journal of medicine and oncology
• Skrajšan naslov: Eurasian j. med. oncol.
• Založnik: AccScience
• ISSN: 2587-196X
• COBISS.SI-ID: 231016707

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.