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TRIM28-dependent developmental heterogeneity determines cancer susceptibility through distinct epigenetic states
Ilaria Panzeri1,2, Luca Fagnocchi3, Stefanos Apostle3
1Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA. ilaria.panzeri@vai.org.
Nature Cancer
|January 24, 2025
Summary
Early-life epigenetic variations, driven by developmental heterogeneity, can establish distinct cancer susceptibility states. This priming influences lifelong cancer risk in individuals carrying cancer predisposition genes.
Area of Science:
- Cancer Biology
- Epigenetics
- Developmental Biology
Background:
- Genetic mutations are necessary for cancer, but not all carriers develop the disease.
- Mechanisms underlying individual cancer susceptibility remain largely unknown.
- Early-life factors may influence long-term cancer risk.
Purpose of the Study:
- To investigate if early-life epigenetic variation impacts cancer susceptibility.
- To explore the role of intrinsic developmental heterogeneity in cancer predisposition.
- To identify potential biomarkers for lifelong cancer risk.
Main Methods:
- Utilized a unique mouse model with intrinsic developmental heterogeneity (Trim28+/D9).
- Analyzed early-life epigenetic states and their association with cancer susceptibility.
- Examined differential methylation patterns in heterochromatin at 10 days of age.
Main Results:
- Heterozygosity of Trim28 created two distinct early-life epigenetic states.
- These states were associated with differing cancer susceptibility.
- Differentially methylated loci were enriched for oncogenes and correlated with poor prognosis in human cancers.
Conclusions:
- Intrinsic developmental heterogeneity can establish lifelong cancer susceptibility.
- Early-life epigenetic priming influences individual cancer risk.
- Epigenetic patterns at heterochromatin may serve as early indicators of cancer predisposition.
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