DNA methylation profiling
Reading chemical tags on DNA that reveal a cell's identity, used to classify brain tumours and to detect cancer in blood.
The Heidelberg/DKFZ methylation classifier is standard for CNS tumour diagnosis (WHO 2021). Methylation in cfDNA underlies Galleri and tissue-of-origin prediction. Nanopore sequencing gives intraoperative methylation classification in under an hour.
How it works
Bisulfite or enzymatic conversion, arrays or sequencing; classifiers trained on reference cohorts.
- Cell-of-origin memory
- Stable analyte in blood
- Reference cohort dependence
A multi-cancer blood test can be run in ordinary clinics, and most positive results can be resolved with imaging. But six in ten positives are false alarms that take months to resolve, and the test misses most cancers. Whether it reduces late-stage cancer or deaths is unknown; that requires randomised trials.
Cancers are defined as much by the tissue they come from as by the mutations they carry, which is why the same drug can work in one organ and fail in another with the same mutation. TCGA is the shared public dataset behind most modern biomarkers and target discovery.
Patients with newly diagnosed glioblastoma who are fit and under about 70 receive six weeks of radiotherapy with daily temozolomide followed by six monthly cycles of temozolomide; this is still the backbone of treatment two decades later. Testing MGMT methylation identifies who benefits most and guides decisions in older patients. Median survival with the regimen remains only around 15-20 months, and no drug since has clearly improved on it, which is why glioblastoma is a priority for new approaches.
Latest papers
topQuery for this technology: (TITLE:"DNA methylation" OR ABSTRACT:"DNA methylation" OR TITLE:"methylation classifier" OR ABSTRACT:"methylation classifier" OR TITLE:"cfDNA methylation" OR ABSTRACT:"cfDNA methylation") 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 DNA methylation profiling, not a curated reading list.
Pages like this
not linked directly; found by shared links- CompanyGRAIL
Shares Track clones in blood with methylation patterns instead of mutations, Pre-agreed update rules so an MCED test is not obsolete when its trial reads out, Prince of Wales Hospital / Chinese University of Hong Kong, Galleri.
- TrialPATHFINDER 2
Shares Pre-agreed update rules so an MCED test is not obsolete when its trial reads out, PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms, Early detection roadmap: organ screening → blood tests for many cancers, Galleri.
- TrialNHS-Galleri
Shares Pre-agreed update rules so an MCED test is not obsolete when its trial reads out, PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms, Early detection roadmap: organ screening → blood tests for many cancers, Galleri.
- TermPositive predictive value (PPV)
Shares Harbinger Health, A urine DNA test to decide who with blood in the urine needs a camera test, PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms, Early detection roadmap: organ screening → blood tests for many cancers.
- TechnologyEpigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)
Shares Switch off an undruggable oncogene permanently with epigenetic editing, Stephen B. Baylin, Hallmark (2022): non-mutational epigenetic reprogramming, USC Norris Comprehensive Cancer Center.
- TermStage shift
Shares Non-endoscopic screening for Barrett's oesophagus and early adenocarcinoma, Molecular indolence classifiers bundled with every screening programme, PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms, Early detection roadmap: organ screening → blood tests for many cancers.
- CollectionNational Brain Tumor Society (NBTS)
Shares H3 K27M (diffuse midline glioma), MGMT promoter methylation, Medulloblastoma, Glioma & glioblastoma.
- ProductAzacitidine
Shares Stephen B. Baylin, USC Norris Comprehensive Cancer Center, Unmask hidden antigens with a short epigenetic course before immunotherapy, Epigenetic reprogramming.