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Instead of reading a few of the tumour's mutations very deeply in blood, read the whole genome once and add up the faint signal from thousands of mutations.
MRDetect (Zviran et al., Nature Medicine 2020) showed that deep sequencing of a small panel is limited by the number of DNA fragments in the tube, and that whole-genome sequencing of cell-free DNA, integrating the signal of thousands of somatic mutations, reached a tumour fraction detection sensitivity as low as 10^-5. MRD-EDGE (Widman et al., Nature Medicine 2024) added machine-learning error suppression that raised single-nucleotide-variant signal-to-noise about 300-fold, cut the aneuploidy needed for copy-number detection from 1 Gb to 200 Mb, detected ctDNA shed by precancerous colorectal adenomas, and allowed plasma-only monitoring without tumour tissue in melanoma and lung cancer on immunotherapy. The commercial descendant of the approach is TrueMRD; AccuScan is a related whole-genome method.
Plasma is sequenced across the whole genome at modest depth; each tumour mutation is seen at most once or twice, and the evidence is summed across thousands of sites, with a classifier separating real tumour fragments from sequencing errors.
A whole-genome blood test for leftover cancer from AccuraGen that corrects sequencing errors read by read, so it can add up thousands of a tumour's mutations.
Whole-genome methods can now follow cancer in blood without a tumour sample. Because each site is read about once, the result is how much tumour DNA there is, not which clone.
It explains why adding sequencing depth to a small panel stops helping, and points to whole-genome and multi-mutation tests as the way to see less tumour DNA.
Query for this technology: (TITLE:"Genome-wide ctDNA mutation integration" OR ABSTRACT:"Genome-wide ctDNA mutation integration" OR TITLE:"MRDetect, MRD-EDGE" OR ABSTRACT:"MRDetect, MRD-EDGE" OR TITLE:"MRDetect" OR ABSTRACT:"MRDetect" OR TITLE:"MRD-EDGE" OR ABSTRACT:"MRD-EDGE") 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 Genome-wide ctDNA mutation integration (MRDetect, MRD-EDGE), not a curated reading list.
Shares Naming which clone or phenotype is left after treatment, Cell-free DNA (cfDNA), Circulating tumour DNA (ctDNA).
Shares AccuScan, Whole-exome & whole-genome sequencing, Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing.
Shares TrueMRD, Whole-exome & whole-genome sequencing, MRD / molecular residual disease testing.
Shares Naming which clone or phenotype is left after treatment, Whole-exome & whole-genome sequencing, Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing.
Shares Naming which clone or phenotype is left after treatment, Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing.
Shares Naming which clone or phenotype is left after treatment, Cell-free DNA (cfDNA), Circulating tumour DNA (ctDNA).
Shares Naming which clone or phenotype is left after treatment, Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing.
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