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Updated: Apr 5, 2026

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Pulmonary Metastases Exhibit Epigenetic Clonality: Implications for Precision Cancer Therapy

Emily S Reardon1, Julie A Hong1, David M Straughan1

  • 1Thoracic Epigenetics Laboratory, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

The Annals of Thoracic Surgery
|August 24, 2015
PubMed
Abstract

Insights

Pulmonary metastases display unique epigenetic profiles, offering potential for targeted therapies. Key epigenetic modifiers like Polycomb repressive complex-2 (PRC-2) are upregulated, suggesting it as a therapeutic target.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Intratumoral heterogeneity limits effective cancer therapies by enabling treatment-resistant clones.
  • Limited data exists on the epigenetic landscapes of pulmonary metastases.
  • Characterizing these epigenetic signatures is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To characterize the epigenetic signatures of pulmonary metastases.
  • To identify potential therapeutic targets within these epigenetic landscapes.

Main Methods:

  • Analyzed RNA and DNA from 65 pulmonary metastases from 12 patients (sarcoma and adrenocortical carcinoma).
  • Evaluated expression of cancer-testis (CT), tumor suppressor (TS), and epigenetic modifier genes using quantitative reverse transcription polymerase chain reaction.
  • Quantitated DNA methylation using pyrosequencing and compared results to normal lung tissues.

Main Results:

  • Pulmonary metastases showed patient-specific global DNA demethylation.
  • Observed significant interpatient heterogeneity in gene expression, despite similar histology.
  • Found consistent epigenetic signatures among metastases from the same patient.
  • Identified upregulation of Polycomb repressive complex-2 (PRC-2) components (EZH2, EED, SUZ12) in most metastases.

Conclusions:

  • Pulmonary metastases exhibit patient-specific epigenetic clonality, exploitable for precision therapies.
  • Targeting aberrant cancer-testis (CT) or tumor suppressor (TS) gene expression is a potential therapeutic strategy.
  • Polycomb repressive complex-2 (PRC-2) represents a potential shared target for epigenetic therapy in pulmonary metastases.

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