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Pulling down DNA in the blood that is still wrapped in the chemical marks of active genes, to see which genes the tumour has switched on, including the targets of some drugs.
Chromatin immunoprecipitation of cell-free nucleosomes carrying active histone marks (cfChIP-seq) was applied to 268 plasma samples by Sadeh and colleagues (Nature Biotechnology 2021), who detected transcriptionally active HER2 amplifications in metastatic colorectal cancer. Baca and colleagues (Nature Medicine 2023) extended it to histone modifications and DNA methylation from 1 mL of plasma, measuring 1,268 epigenomic profiles from 433 people with 15 cancers, and inferred the expression of diagnostic markers and drug targets and the activity of targetable transcription factors. In the full text, samples were analysed only above 3 per cent ctDNA (5 per cent for ERBB2), the level to which the tumour-fraction estimator is benchmarked, and the oestrogen receptor comparisons involved 17 to 19 patients. TROP2 (TACSTD2) is not among the genes reported.
Antibodies against marks of active promoters and enhancers (H3K4me3, H3K27ac) capture the nucleosomes that carried them in the dying cell; sequencing what is captured maps which genes were active in the cells shedding DNA.
Blood can show what a tumour is doing, not only what mutations it has. It is a proof of concept in advanced cancer.
The first demonstration that gene activity in the tissue of origin can be read from nucleosomes in blood.
Query for this technology: (TITLE:"Plasma epigenomic profiling" OR ABSTRACT:"Plasma epigenomic profiling" OR TITLE:"cfChIP-seq" OR ABSTRACT:"cfChIP-seq" OR TITLE:"ChIP-seq of plasma cell-free nucleosomes" OR ABSTRACT:"ChIP-seq of plasma cell-free nucleosomes" OR TITLE:"Liquid biopsy epigenomic profiling" OR ABSTRACT:"Liquid biopsy epigenomic profiling") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Plasma epigenomic profiling (cfChIP-seq), not a curated reading list.
Shares Griffin (nucleosome profiling of cell-free DNA), Naming which clone or phenotype is left after treatment, Cell-free DNA (cfDNA), DNA methylation profiling.
Shares Naming which clone or phenotype is left after treatment, Cell-free DNA (cfDNA), Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).
Shares EPIC-seq (expression inference from cell-free DNA), Cell-free DNA (cfDNA), Circulating tumour DNA (ctDNA).
Shares Griffin (nucleosome profiling of cell-free DNA), Cell-free DNA (cfDNA), Circulating tumour DNA (ctDNA).
Shares Cell-free DNA (cfDNA), Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).
Shares Cell-free DNA (cfDNA), DNA methylation profiling, Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).
Shares Cell-free DNA (cfDNA), DNA methylation profiling, Circulating tumour DNA (ctDNA).
Shares Cell-free DNA (cfDNA), DNA methylation profiling, Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).
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