{"entity":{"id":"idea-bio1-methylation-clone-tracking","kind":"idea","name":"Track clones in blood with methylation patterns instead of mutations","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["methylation-profiling","liquid-biopsy"],"targets":[],"drugs":[],"companies":["grail"],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"small","horizonYears":3},"route":"/ideas/idea-bio1-methylation-clone-tracking/","neighbours":{"technology":[{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"company":[{"id":"grail","kind":"company","name":"GRAIL","route":"/companies/grail/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"bottleneck":[{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"roadmap":[{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"}]}}