Where Methylation Happens

Same CH₃, different meaning — it depends on the genomic region.

🎮
Simulation

Receive a clinical case, choose the right region and methylation level — and grade your answer.

Gene model
PromoterEnhancerGene bodyLINE-1
Promoter CpG island
Methylation level50%
Gene expression53%
Key lesson: Hypermethylation is not always bad. Hypomethylation is not always good. What matters is WHERE the CH₃ lands and WHICH gene it affects.
Examples in this region
BRCA1DNA repair / tumor suppressor
Hyper: Silencing → breast cancer, ovarian cancer, triple-negative tumors, Fanconi-like phenotypes.
Hypo: Preserved repair → low risk of hereditary-like breast/ovarian cancer.
MLH1Mismatch repair
Hyper: Loss of MMR → sporadic Lynch-like colorectal cancer, endometrial cancer, gastric cancer (MSI-high).
Hypo: Active MMR → reduced risk of MSI tumors and colorectal cancer.
MGMTRemoves alkyl DNA damage
Hyper: Silencing → glioblastoma, colorectal cancer; paradoxically ↑ response to temozolomide chemotherapy.
Hypo: Active repair → protection against alkylating-agent mutagenesis and secondary tumors.
CDKN2A (p16)Cell-cycle brake / tumor suppressor
Hyper: Silencing → melanoma, pancreatic cancer, non-small cell lung cancer, head & neck squamous cell carcinoma, leukemia.
Hypo: Active p16 → senescence on demand, lower risk of melanoma and pancreatic cancer.
RASSF1ARas signaling regulator
Hyper: Silencing → breast, lung, prostate, kidney, and hepatocellular cancers (>50% of solid tumors).
Hypo: Ras pathway controlled → normal apoptosis, lower solid-tumor risk.
GSTP1Phase II detox / glutathione transferase
Hyper: Silencing → prostate cancer (hallmark biomarker), hepatocellular carcinoma, breast cancer.
Hypo: Active detox → protection against carcinogen-induced prostate and liver cancer.
APCWnt pathway brake / tumor suppressor
Hyper: Silencing → colorectal cancer, gastric cancer, hepatoblastoma, desmoid tumors.
Hypo: Balanced Wnt → intestinal homeostasis, reduced colorectal cancer risk.
What this means

Promoter hypermethylation often reduces gene expression. If this happens in protective genes — DNA repair or tumor suppressors — the cell may lose part of its natural protection.

🎮 Clinical game

Get a case, pick the right region and methylation level.