OnCo
ideasIdea

Track clones in blood with methylation patterns instead of mutations

Tumour DNA in blood can be told apart by chemical marks as well as mutations. Marks are more numerous and cheaper to read, so they could track more sub-populations for less money.

Mutation-based clone tracking needs deep whole-exome or genome sequencing of tumour and plasma. Methylation haplotypes are clone-stable, abundant, and readable with targeted enrichment at lower cost. The proposal is to define clone-specific methylation haplotypes from multi-region tumour tissue and monitor their plasma fractions as a low-cost clonal evolution assay.

Hypothesis
Methylation-haplotype clone tracking recapitulates mutation-defined clonal dynamics in plasma with at least 80 percent concordance at a fifth of the sequencing cost.
Rationale
Methylation is used for cancer signal origin in multi-cancer detection tests and is clonally heritable; epiallele heterogeneity has been shown to track evolution in leukaemias.
What would test it
Paired analysis on 50 patients with existing multi-region WGS and serial plasma: derive methylation clone markers and compare trajectories with the mutation-based phylogenies.
Maturity
speculative
Who has to act
research
Cost to try
Small (under $1M)
Years to first evidence
3
Bottlenecks it attacks

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