# Track clones in blood with methylation patterns instead of mutations

Source: https://onco.cc/ideas/idea-bio1-methylation-clone-tracking/  
OnCo record `idea-bio1-methylation-clone-tracking` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: research

## Sources

- Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012): https://doi.org/10.1056/NEJMoa1113205

## Connected records

- technologies: [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- companies: [GRAIL](https://onco.cc/companies/grail/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/)
- bottlenecks: [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/)

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