Profiling of Epigenetic Features in Clinical Samples Reveals Novel Widespread Changes in Cancer

Area of Science:

• Epigenetics and Cancer Biology
• Mass Spectrometry in Proteomics

Background:

• Aberrant histone post-translational modifications (PTMs) and histone modifying enzymes (HMEs) are implicated in numerous cancers.
• Understanding these epigenetic alterations is crucial for identifying cancer biomarkers and therapeutic targets.

Purpose of the Study:

• To comprehensively profile histone H3 PTMs in normal and tumor tissues across various cancer types.
• To identify tumor-specific and general epigenetic changes associated with cancer development.
• To explore the potential of histone PTMs as cancer biomarkers and therapeutic targets.

Main Methods:

• Utilized mass spectrometry-based approaches for in-depth analysis of histone H3 PTMs.
• Compared PTM profiles between normal tissues and multiple cancer types.
• Correlated observed PTM changes with gene expression data of HMEs from public databases.

Main Results:

• Identified diverse histone H3 PTM changes in tumors, some proliferation-dependent and others cell-cycle independent.
• Observed partial correlation between tumor PTM profiles and HME gene expression, with changes often lost in cell culture.
• Discovered tumor- and subtype-specific PTM alterations, alongside a consistent decrease in histone H3 K9me3 and K14ac across models.

Conclusions:

• Histone PTM profiling provides insights into cancer-specific epigenetic landscapes.
• The cell-cycle independent decrease in H3K14ac across multiple cancer models suggests it as a potential novel epigenetic hallmark of cancer.
• These findings support the role of epigenetics in cancer and highlight potential avenues for biomarker discovery and targeted therapies.