# DNA methylation profiling

Source: https://onco.cc/technologies/methylation-profiling/  
OnCo record `methylation-profiling` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Reading chemical tags on DNA that reveal a cell's identity, used to classify brain tumours and to detect cancer in blood.

## Summary

DNA methylation profiling reads the chemical marks on cytosines that record a cell's identity, using bisulfite or enzymatic conversion followed by arrays or sequencing, with classifiers trained on reference cohorts. The Heidelberg/DKFZ methylation classifier is standard for CNS tumour diagnosis (WHO 2021) because methylation retains cell-of-origin memory even when histology is ambiguous. Methylation in cfDNA underlies Galleri and tissue-of-origin prediction, since it is a stable analyte in blood. Nanopore sequencing gives intraoperative methylation classification in under an hour, allowing the surgical plan to change during the operation. The main limitation is dependence on the reference cohort, so rare or under-represented tumour types can be misclassified. The simple version is that methylation is a cell's identity badge, readable in tissue or blood.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-04
- Principle: Bisulfite or enzymatic conversion, arrays or sequencing; classifiers trained on reference cohorts.
- Strengths: Cell-of-origin memory; Stable analyte in blood
- Limitations: Reference cohort dependence

## Notes

- Colorectal cancer: methylation is a cause here, not just a marker. CIMP-positive tumours are a distinct subset encompassing almost all BRAF-mutant cancers (odds ratio 203), and sporadic mismatch repair deficiency arises almost exclusively from CIMP-associated MLH1 promoter methylation (Weisenberger 2006), which is reversible in cell lines (Herman 1998). MLH1 promoter methylation testing is the routine clinical use.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/DNA_methylation
- Wikipedia: https://en.wikipedia.org/wiki/DNA_methylation

## Connected records

- technologies: [Bladder EpiCheck urine methylation test](https://onco.cc/technologies/bladder-epicheck/), [Cell-free DNA methylation tests](https://onco.cc/technologies/cfdna-methylation-testing/), [Long-read sequencing (PacBio, Oxford Nanopore)](https://onco.cc/technologies/long-read-sequencing/), [Methylation classifier for brain tumours](https://onco.cc/technologies/cns-tumour-methylation-classifier/), [Methylation classifier for sarcomas](https://onco.cc/technologies/sarcoma-methylation-classifier/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/), [Urine tests for bladder cancer (cytology, FISH, RNA and methylation)](https://onco.cc/technologies/urine-bladder-cancer-tests/)
- cancers: [Astrocytoma, IDH-mutant (grades 2 to 4)](https://onco.cc/cancers/idh-mutant-astrocytoma/), [Atypical teratoid/rhabdoid tumour (ATRT)](https://onco.cc/cancers/atrt/), [Cancer of unknown primary (CUP)](https://onco.cc/cancers/cancer-of-unknown-primary/), [Cancer of unknown primary, favourable subsets](https://onco.cc/cancers/cup-favourable-subsets/), [Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma)](https://onco.cc/cancers/cup-unfavourable/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Diffuse midline glioma, H3 K27-altered (including DIPG)](https://onco.cc/cancers/dipg-dmg/), [Ependymoma](https://onco.cc/cancers/ependymoma/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)](https://onco.cc/cancers/medulloblastoma-group-3-4/), [Medulloblastoma](https://onco.cc/cancers/medulloblastoma/), [Meningioma](https://onco.cc/cancers/meningioma/), [Oligodendroglioma, IDH-mutant and 1p/19q-codeleted](https://onco.cc/cancers/oligodendroglioma/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/), [Paediatric low-grade glioma](https://onco.cc/cancers/paediatric-low-grade-glioma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [SHH-activated medulloblastoma](https://onco.cc/cancers/medulloblastoma-shh/), [Spinal cord tumours (intramedullary and intradural)](https://onco.cc/cancers/spinal-cord-tumours/), [WNT-activated medulloblastoma](https://onco.cc/cancers/medulloblastoma-wnt/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- companies: [Adela](https://onco.cc/companies/adela/), [Clear Gene](https://onco.cc/companies/clear-gene/), [ClearNote Health](https://onco.cc/companies/clearnote-health/), [Freenome](https://onco.cc/companies/freenome/), [Harbinger Health](https://onco.cc/companies/harbinger-health/), [Helio Genomics](https://onco.cc/companies/helio-genomics/), [Nucleix](https://onco.cc/companies/nucleix/), [Oxford Nanopore Technologies](https://onco.cc/companies/oxford-nanopore/), [Universal DX](https://onco.cc/companies/universal-dx/)
- key papers: [Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set](https://onco.cc/key-papers/paper-klein-ccga3-mced-validation-ann-oncol-2021/), [Comprehensive genomic characterization of squamous cell lung cancers](https://onco.cc/key-papers/paper-tcga-lung-squamous-nature-2012/), [Comprehensive molecular characterization of human colon and rectal cancer](https://onco.cc/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/), [Comprehensive molecular profiling of lung adenocarcinoma](https://onco.cc/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/), [CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer](https://onco.cc/key-papers/paper-weisenberger-cimp-braf-mlh1-colorectal-nat-genet-2006/), [Detecting neuroendocrine prostate cancer through tissue-informed cell-free DNA methylation analysis](https://onco.cc/key-papers/paper-berchuck-cfdna-methylation-nepc-detection-ccr-2022/), [Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer](https://onco.cc/key-papers/paper-beltran-nepc-divergent-evolution-nat-med-2016/), [Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma](https://onco.cc/key-papers/paper-herman-mlh1-promoter-hypermethylation-colorectal-pnas-1998/), [Pancreatic cancer early detection biomarkers for high-risk individuals: insights from the PRECEDE consortium](https://onco.cc/key-papers/paper-worthington-precede-early-detection-biomarkers-ijc-2026/), [PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms](https://onco.cc/key-papers/paper-pathfinder-lancet-2023/), [Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial](https://onco.cc/key-papers/paper-nhs-galleri-performance-nat-med-2026/), [Stupp 2005: temozolomide added to radiotherapy for newly diagnosed glioblastoma](https://onco.cc/key-papers/paper-stupp-temozolomide-nejm-2005/), [TCGA Pan-Cancer Atlas: 10,000 tumours across 33 cancer types, classified by molecular features](https://onco.cc/key-papers/paper-tcga-pancancer-atlas-cell-2018/)
- terms: [CCGA: the Circulating Cell-free Genome Atlas behind the Galleri methylation test](https://onco.cc/terms/ccga-study/), [DNA methylation arrays and beta values (450k, EPIC)](https://onco.cc/terms/methylation-arrays/), [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/), [H3 K27M (diffuse midline glioma)](https://onco.cc/terms/h3k27m/), [Hallmark (2022): non-mutational epigenetic reprogramming](https://onco.cc/terms/nonmutational-epigenetic-reprogramming/), [MGMT promoter methylation](https://onco.cc/terms/mgmt/)
- ideas: [A ten-dollar blood test for the five cancers that kill most people in poorer countries](https://onco.cc/ideas/idea-prev-lmic-five-cancer-methylation-test/), [A urine DNA test to decide who with blood in the urine needs a camera test](https://onco.cc/ideas/idea-prev-urine-dna-haematuria-triage/), [Blood-based HCC surveillance to replace six-monthly ultrasound](https://onco.cc/ideas/idea-hcc-blood-surveillance/), [Match each blood-detected clone to the lesion it comes from on the scan](https://onco.cc/ideas/idea-bio1-clone-to-lesion-mapping/), [Molecular indolence classifiers bundled with every screening programme](https://onco.cc/ideas/idea-moon-indolence-classifiers-with-screening/), [Non-endoscopic screening for Barrett's oesophagus and early adenocarcinoma](https://onco.cc/ideas/idea-non-endoscopic-barretts-screening/), [Post every woman an HPV self-test kit instead of asking her to book a smear](https://onco.cc/ideas/idea-prev-hpv-self-sampling-mailed-default/), [Pre-agreed update rules so an MCED test is not obsolete when its trial reads out](https://onco.cc/ideas/idea-prev-mced-change-control-plan/), [Push residual disease detection a hundredfold deeper with whole-genome methods](https://onco.cc/ideas/idea-bio2-whole-genome-mrd-depth/), [Switch off an undruggable oncogene permanently with epigenetic editing](https://onco.cc/ideas/idea-bio1-epigenetic-silencing-in-vivo/), [Track clones in blood with methylation patterns instead of mutations](https://onco.cc/ideas/idea-bio1-methylation-clone-tracking/), [Unmask hidden antigens with a short epigenetic course before immunotherapy](https://onco.cc/ideas/idea-bio2-epigenetic-priming-cold-tumours/)
- drugs: [Cancerguard](https://onco.cc/drugs/cancerguard/), [Cologuard](https://onco.cc/drugs/cologuard/), [Cologuard Plus](https://onco.cc/drugs/cologuard-plus/), [Galleri](https://onco.cc/drugs/galleri/), [Guardant Reveal](https://onco.cc/drugs/guardant-reveal/), [SimpleScreen CRC](https://onco.cc/drugs/simplescreen-crc/)
- institutions: [Case Comprehensive Cancer Center](https://onco.cc/institutions/case-ccc/), [Garvan Institute of Medical Research / Kinghorn Cancer Centre](https://onco.cc/institutions/garvan-institute/), [German Cancer Research Center (DKFZ)](https://onco.cc/institutions/dkfz/), [Heidelberg University Hospital / NCT / DKFZ](https://onco.cc/institutions/heidelberg-nct/), [Instituto Português de Oncologia do Porto Francisco Gentil](https://onco.cc/institutions/ipo-porto/), [Prince of Wales Hospital / Chinese University of Hong Kong](https://onco.cc/institutions/prince-of-wales-hospital-cuhk/), [Sydney Children's Hospitals Network / Children's Cancer Institute](https://onco.cc/institutions/sydney-childrens-hospitals-network/), [USC Norris Comprehensive Cancer Center](https://onco.cc/institutions/usc-norris/)
- trials: [BLUE-C](https://onco.cc/trials/blue-c/), [DeeP-C](https://onco.cc/trials/deep-c/), [NHS-Galleri](https://onco.cc/trials/nhs-galleri/), [PATHFINDER 2](https://onco.cc/trials/pathfinder-2/), [PREEMPT CRC](https://onco.cc/trials/preempt-crc/)
- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/), [Diagnostics roadmap: stains → gene panels → blood tests that decide treatment](https://onco.cc/roadmaps/diagnostics-roadmap/), [Early detection roadmap: organ screening → blood tests for many cancers](https://onco.cc/roadmaps/early-detection-roadmap/), [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)
- collections: [TCGA / NCI Genomic Data Commons](https://onco.cc/collections/tcga-gdc/)
- people: [Amar Gajjar](https://onco.cc/people/amar-gajjar/), [Andreas von Deimling](https://onco.cc/people/andreas-von-deimling/), [Eric A. Klein](https://onco.cc/people/eric-klein/), [Ian Cree](https://onco.cc/people/cree-ian/), [Michael D. Taylor](https://onco.cc/people/michael-taylor/), [Monika E. Hegi](https://onco.cc/people/monika-hegi/), [Stefan Pfister](https://onco.cc/people/stefan-pfister/), [Stephen B. Baylin](https://onco.cc/people/stephen-baylin/)
- bottlenecks: [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/)
- pathways: [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/)

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