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Updated: May 16, 2025
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Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression
Published on: August 28, 2012
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Endometrial tumorigenesis involves epigenetic plasticity demarcating non-coding somatic mutations and 3D-genome
Sebastian Gregoricchio1, Aleksandar Kojic2, Marlous Hoogstraat2,3
1Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. s.gregoricchio@nki.nl.
Genome Biology
|May 9, 2025
Summary
Endometrial cancer (EC) growth is driven by estrogen receptor alpha (ERα). This study reveals how 3D genome changes and mutations enhance ERα expression, driving EC progression.
Area of Science:
- Genomics
- Epigenetics
- Cancer Biology
Background:
- Endometrial cancer (EC) incidence and mortality are increasing.
- Estrogen receptor alpha (ERα) drives proliferation in 85% of EC cases.
- Transcriptional regulation of ERα in EC remains poorly understood.
Purpose of the Study:
- Investigate the transcriptional regulation of ERα in endometrial cancer.
- Elucidate the role of 3D genome organization and epigenetic alterations in EC development.
- Identify genetic and epigenetic factors contributing to EC progression.
Main Methods:
- Generation of epigenomics, transcriptomics, and Hi-C data from healthy and tumor endometrial tissues.
- Integration of EC risk single-nucleotide polymorphisms and whole-genome sequencing data.
- Machine learning predictions and interaction proteomics analyses.
Main Results:
- Identified significant ERα reprogramming and altered 3D genome organization in EC.
- Discovered tumor-specific enhancer activity and enrichment of risk variants at ERα sites.
- Uncovered an enhancer mutation impairing EHMT2/G9a/KMT1C recruitment, reducing ERα repression.
Conclusions:
- A complex genomic-epigenomic interplay drives EC development and progression.
- Altered 3D genome organization enhances the expression of ERα, a key driver in EC.
- Findings provide insights into the molecular mechanisms underlying EC pathogenesis.
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