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High YEATS4 expression characterizes MDM2-amplified liposarcoma.

Andrea Mariani1, Mika Sampo2, Harri Sihto1

  • 1Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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|August 21, 2025
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Summary
This summary is machine-generated.

YEATS4 gene expression is elevated in liposarcomas (LPS), particularly in MDM2-amplified and high-grade dedifferentiated subtypes. Silencing YEATS4 reduced cancer cell viability, suggesting its role in LPS progression and potential as a therapeutic target.

Keywords:
MDM2YEATS4liposarcomareal-time PCR

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • YEATS4 is located in the 12q13-15 region, often co-amplified with MDM2 and CDK4 in liposarcomas (LPS).
  • The specific role of YEATS4 in LPS development and dedifferentiation is not well understood.

Purpose of the Study:

  • To investigate the expression of YEATS4 in liposarcoma samples.
  • To determine the functional significance of YEATS4 in liposarcoma progression and dedifferentiation.

Main Methods:

  • Quantitative real-time PCR and fluorescence in situ hybridization (FISH) were used to analyze YEATS4 expression and MDM2 amplification in 57 LPS samples.
  • siRNA-mediated knockdown of YEATS4 was performed in two well-differentiated LPS cell lines (GOT-3 and 93T449).

Main Results:

  • YEATS4 mRNA levels were significantly higher in MDM2-positive LPS tumors compared to MDM2-negative tumors (p = 0.008).
  • High YEATS4 expression was observed in 64% of high-grade dedifferentiated LPS (DDLPS), 54% of low-grade DDLPS, and 29% of well-differentiated LPS (WDLPS).
  • YEATS4 knockdown reduced cell viability in 93T449 cells by 24.1% at Day 5 and 22.1% at Day 7 (p < 0.001).

Conclusions:

  • YEATS4 may contribute to liposarcoma progression, especially in MDM2-amplified and high-grade DDLPS.
  • The varied functional impact of YEATS4 suggests complexity within the 12q13-15 amplicon.
  • YEATS4 warrants further investigation as a potential biomarker and therapeutic target for LPS.