Cancer Epigenetics and Chromatin Regulators
Epigenetic systems control which genes are accessible without changing the DNA sequence. Cancer can alter the enzymes that write, erase or read chromatin marks, the complexes that move nucleosomes, and the distribution of DNA methylation itself.
Quick answer
An epigenetic change is not automatically reversible, targetable or caused by a single mutation. Interpretation starts by separating the altered layer—DNA methylation, a histone mark, a chromatin complex or a lineage programme—and then asking how it was measured.
How the cluster fits together
Key gene profiles
Epigenetics and chromatin library
Follow chromatin marks from mechanism to disease context and emerging treatment strategies.
DNMT3A and TET2 in Clonal Haematopoiesis
How age-related mutations in the DNA-methylation regulators DNMT3A and TET2 expand blood cell clones, what clonal haematopoiesis of indeterminate potential means, and its known risks.
3 min readEZH2 and Polycomb Repression in Cancer
How EZH2, the enzymatic core of polycomb repressive complex 2, silences genes through H3K27 methylation, why it can act as an oncogene or a tumour suppressor, and where inhibitors are used.
3 min readKMT2D and KMT2C: Enhancer Regulators Lost in Many Cancers
Why the histone methyltransferases KMT2D and KMT2C are among the most frequently mutated genes across cancer, how they mark active enhancers, and what loss means for interpretation.
3 min readKDM6A (UTX): An X-Linked Histone Demethylase Tumour Suppressor
How KDM6A removes the repressive H3K27me3 mark, why its location on the X chromosome contributes to sex differences in some cancers, and where its loss is common.
3 min readSETD2: H3K36 Methylation, Transcription and Repair
How SETD2 writes the H3K36me3 mark that guides transcription, splicing and DNA repair, and why its loss is a recurrent event in clear cell renal cell carcinoma and other cancers.
3 min readBAP1 Tumour Predisposition Syndrome
How germline BAP1 loss predisposes to mesothelioma, uveal melanoma, renal cell carcinoma and distinctive skin tumours, and how somatic BAP1 loss is used in pathology.
3 min readHistone H3 K27M and Diffuse Midline Glioma
How a single lysine-to-methionine change in histone H3 reprogrammes the epigenome of diffuse midline glioma, why it defines the tumour type, and what is being tried therapeutically.
3 min readHistone H3 G34 Mutations in Paediatric High-Grade Glioma
How glycine-34 substitutions in histone H3.3 define a distinct group of hemispheric paediatric high-grade gliomas, how they differ from K27M, and their effect on chromatin and repair.
3 min readBET Bromodomain Inhibitors: Targeting Transcriptional Addiction
How BET proteins such as BRD4 read acetylated histones to drive transcription of genes like MYC, why BET inhibitors were developed, and the challenges seen in trials.
3 min readHDAC Inhibitors in Cancer: Where They Work and Where They Do Not
How histone deacetylase inhibitors change gene expression, why they are approved mainly in T-cell lymphomas and myeloma, and why they have underperformed in solid tumours.
3 min readDNA Methylation in Cancer: Silencing and Instability
How cancers combine focal promoter hypermethylation that silences tumour suppressors with genome-wide hypomethylation, and how methylation is used for classification and detection.
3 min readThe CpG Island Methylator Phenotype (CIMP)
What it means when a tumour has widespread coordinated promoter methylation, how CIMP relates to BRAF mutation and MLH1 silencing in colorectal cancer, and its limits as a category.
3 min readMenin-KMT2A Inhibitors in Acute Leukaemia
How KMT2A rearrangements and NPM1 mutations create a dependence on the menin-KMT2A interaction, and how menin inhibitors such as revumenib exploit it.
3 min readSMARCB1 Loss and Rhabdoid Tumours
How loss of the SWI/SNF subunit SMARCB1 causes rhabdoid tumours despite a near-silent genome, the link to the rhabdoid predisposition syndrome, and the EZH2 dependency it creates.
3 min readHypomethylating Agents: Azacitidine and Decitabine
How azacitidine and decitabine deplete DNMT enzymes to reverse aberrant DNA methylation, where they are used in myeloid disease, and why response takes months.
3 min readFrequently asked questions
What is the difference between a genetic and an epigenetic change?
A genetic change alters DNA sequence or structure; an epigenetic change alters how DNA is packaged or regulated without necessarily changing its sequence.
Does promoter methylation always switch a gene off?
No. The genomic region, assay, cut-off, cellular mixture and relationship between methylation and expression all affect interpretation.
Are all chromatin-regulator mutations targetable?
No. Some create established treatment contexts, while many remain biological markers or research hypotheses rather than validated treatment biomarkers.