CTNNB1 mutation represents a recurrent driver molecular alteration in a subset of endometrial stromal tumors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F26%3A10001459" target="_blank" >RIV/00064190:_____/26:10001459 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1007/s00428-026-04420-6" target="_blank" >https://doi.org/10.1007/s00428-026-04420-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00428-026-04420-6" target="_blank" >10.1007/s00428-026-04420-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

CTNNB1 mutation represents a recurrent driver molecular alteration in a subset of endometrial stromal tumors

Popis výsledku v původním jazyce

Low-grade endometrial stromal sarcomas (LGESS) and endometrial stromal nodules represent a distinct entity with characteristic morphology, immunohistochemical profile, and molecular features. It has been suggested that the activation of the Wnt signaling pathway is a potential driver in some of these tumors. Approximately 70-75% of LGESS are characterized by non-random recurrent fusions mostly involving JAZF1 and PHF1 genes. Although the exact mechanism remains unclear, activation of the Wnt signaling pathway appears to be related to the functional deregulation of chromatin remodeling complexes caused by these fusion proteins. However, knowledge about other possible mechanisms and recurrent molecular alterations occurring at the DNA level in LGESS remains limited. We report three cases of LGESS in patients aged 39, 49, and 50, lacking recurrent fusions but harboring CTNNB1 mutations in exon 3 as the sole detectable molecular alteration. One case had morphological features of typical LGESS (in some areas with perivascular whorling, which was not a dominant feature), the second case showed features of the fibroblastic variant of LGESS, and the third case comprised a LGESS with a peculiar morphology with diffuse whorling morphologically identical to the recently described entity endometrial stromal tumor with GREB1::CTNNB1 fusion. RNA-Seq-based clustering analysis of the three cases and a set of 193 uterine tumors showed that the CTNNB1-mutated cases clustered near LGESS cases. This study adds to the growing body of evidence that CTNNB1 mutations represent a driver molecular event in a small subset of endometrial stromal tumors. Moreover, the results of our study suggest that tumors with CTNNB1 mutation and GREB1::CTNNB1 fusion may exhibit identical morphology and potentially represent the same category of tumor. Characterization and reporting of additional cases are needed to determine whether these are part of the spectrum of low-grade endometrial stromal tumors (either endometrial stromal nodule or LGESS) or represent a separate category of tumors characterized by CTNNB1 alteration as a driver event.

Název v anglickém jazyce

CTNNB1 mutation represents a recurrent driver molecular alteration in a subset of endometrial stromal tumors

Popis výsledku anglicky

Low-grade endometrial stromal sarcomas (LGESS) and endometrial stromal nodules represent a distinct entity with characteristic morphology, immunohistochemical profile, and molecular features. It has been suggested that the activation of the Wnt signaling pathway is a potential driver in some of these tumors. Approximately 70-75% of LGESS are characterized by non-random recurrent fusions mostly involving JAZF1 and PHF1 genes. Although the exact mechanism remains unclear, activation of the Wnt signaling pathway appears to be related to the functional deregulation of chromatin remodeling complexes caused by these fusion proteins. However, knowledge about other possible mechanisms and recurrent molecular alterations occurring at the DNA level in LGESS remains limited. We report three cases of LGESS in patients aged 39, 49, and 50, lacking recurrent fusions but harboring CTNNB1 mutations in exon 3 as the sole detectable molecular alteration. One case had morphological features of typical LGESS (in some areas with perivascular whorling, which was not a dominant feature), the second case showed features of the fibroblastic variant of LGESS, and the third case comprised a LGESS with a peculiar morphology with diffuse whorling morphologically identical to the recently described entity endometrial stromal tumor with GREB1::CTNNB1 fusion. RNA-Seq-based clustering analysis of the three cases and a set of 193 uterine tumors showed that the CTNNB1-mutated cases clustered near LGESS cases. This study adds to the growing body of evidence that CTNNB1 mutations represent a driver molecular event in a small subset of endometrial stromal tumors. Moreover, the results of our study suggest that tumors with CTNNB1 mutation and GREB1::CTNNB1 fusion may exhibit identical morphology and potentially represent the same category of tumor. Characterization and reporting of additional cases are needed to determine whether these are part of the spectrum of low-grade endometrial stromal tumors (either endometrial stromal nodule or LGESS) or represent a separate category of tumors characterized by CTNNB1 alteration as a driver event.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2026

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

VIRCHOWS ARCHIV

ISSN

0945-6317

e-ISSN

1432-2307

Svazek periodika

488

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

661-669

Kód UT WoS článku

001672714100001

EID výsledku v databázi Scopus

2-s2.0-105028884002