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GREB1-rearranged uterine tumour shares a common DNA methylation signature with ESR1-rearranged UTROSCT

Background and objectives GREB1-rearranged uterine tumours encompass a group of uterine mesenchymal tumours with varied histologic appearances. The fusion partners to GREB1 include NCOA1-3, SS18 and NR4A3. Given that some GREB1-rearranged uterine tumours exhibit histologic features of uterine tumour...

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Auteurs principaux: Lee, Cheng-Han (Auteur) , Lee, Yow-Shan (Auteur) , Bennett, Jennifer A. (Auteur) , Kolin, David L. (Auteur) , Lee, Jen-Chieh (Auteur) , Huang, Hsuan-Ying (Auteur) , Köbel, Martin (Auteur) , Sementsov, Mark (Auteur) , Dickson, Brendan C. (Auteur) , Kölsche, Christian (Auteur) , Kommoss, Friedrich (Auteur) , Deimling, Andreas von (Auteur) , Kommoss, Felix (Auteur)
Format: Article (Journal)
Langue:anglais
Publié: 2026
In: Histopathology
Year: 2026, Volume: 88, Numéro: 5, Pages: 1084-1093
ISSN:1365-2559
DOI:10.1111/his.70075
Accès en ligne:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/his.70075
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/his.70075
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Notes sur l'auteur:Cheng-Han Lee, Yow-Shan Lee, Jennifer A Bennett, David L Kolin, Jen-Chieh Lee, Hsuan-Ying Huang, Martin Köbel, Mark Sementsov, Brendan C Dickson, Christian Koelsche, Friedrich Kommoss, Andreas von Deimling & Felix K F Kommoss
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Résumé:Background and objectives GREB1-rearranged uterine tumours encompass a group of uterine mesenchymal tumours with varied histologic appearances. The fusion partners to GREB1 include NCOA1-3, SS18 and NR4A3. Given that some GREB1-rearranged uterine tumours exhibit histologic features of uterine tumours resembling ovarian sex cord tumour (UTROSCT), there is a general belief that GREB1-rearranged uterine mesenchymal tumours are part of the UTROSCT family. Methods In this study, we applied global DNA methylation and copy number analyses to a series of 10 GREB1-rearranged uterine tumours and 21 classic UTROSCTs (7 of which were molecularly confirmed to harbour ESR1::NCOA2/3 fusions). Results We found that GREB1-rearranged uterine tumors show an overlap in their global methylation profiles with UTROSCT, including ESR1::NCOA2/3 positive cases. Together, these tumours form a DNA methylation cluster separate from uterine smooth muscle tumours (leiomyomas and leiomyosarcomas), endometrial stromal sarcomas (low-grade and high-grade), embryonal rhabdomyosarcoma and SMARCA4-deficient uterine sarcomas. However, despite their epigenetic similarity, there were two notable differences. First, GREB1-rearranged uterine tumours as a group displayed a greater degree of genomic complexity with more extensive copy number alterations than conventional UTROSCTs, including those harbouring ESR1::NCOA2/3. Second, GREB1-rearranged uterine tumours frequently lacked overt sex cord morphology: while all 7 ESR1::NCOA2/3 UTROSCTs demonstrated corded, nested, trabecular and/or tubular/sertoliform patterns, only 1 GREB1-rearranged uterine tumour displayed a prominent trabecular pattern, with the remaining cases showing exclusively or predominantly diffuse/solid growth. Conclusions Overall, our findings confirm that GREB1-rearranged uterine tumours are part of the UTROSCT spectrum, though they frequently exhibit a more diffuse growth pattern and a higher degree of genomic instability.
Description:Online veröffenrlicht: 22 December 2025
Gesehen am 22.06.2026
Description matérielle:Online Resource
ISSN:1365-2559
DOI:10.1111/his.70075

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