Liquid biopsy epigenomic profiling for cancer subtyping.

Area of Science:

• Oncology
• Epigenetics
• Molecular Biology

Background:

• Circulating tumor DNA (ctDNA) assays are valuable in cancer care but cannot fully capture cancer's transcriptional programs.
• Dynamic changes in cancer phenotypes and gene expression are crucial for understanding disease progression and treatment response.

Purpose of the Study:

• To develop a method for comprehensive epigenomic profiling of cancer directly from patient plasma.
• To assess the potential of plasma epigenomics to provide clinically actionable information non-invasively.

Main Methods:

• Developed an immunoprecipitation-based assay to profile histone modifications and DNA methylation in 1 ml of plasma.
• Analyzed 1,268 epigenomic profiles from 433 individuals across 15 different cancer types.
• Validated the assay as a proxy for transcriptional activity.

Main Results:

• Plasma epigenomic profiling robustly reflects transcriptional activity in cancer.
• The method successfully inferred expression levels of diagnostic markers and drug targets.
• Detected therapeutically relevant transcription factor activity and epigenetic mechanisms of resistance.

Conclusions:

• Plasma epigenomic profiling offers a powerful, non-invasive alternative to tissue biopsies for comprehensive cancer analysis.
• This approach has the potential to unlock critical, actionable insights into cancer biology and treatment resistance from blood samples.