AMED3001 Cancer
Cancer Gene Activation, Epigenetics & Driver Pathways
Week 7 explains how cancer genes are switched on and off beyond simple mutation, and maps the driver pathways that recur across cancers. It covers viral oncogenesis (HPV E6/E7), epigenetic dysregulation (promoter hypermethylation silencing tumour suppressors), non-coding-RNA control, and the RTK-RAS-MAPK, PI3K-AKT and Wnt/APC/β-catenin pathways. Drawing a pathway and explaining epigenetic silencing are flagship short-answer and diagram tasks in the final (50%, confirm on Canvas).
What this chapter covers
- 01Viral oncogenesis: viral genome integration; HPV E6 → degrades p53, E7 → degrades pRb; insertional mutagenesis driving c-myc
- 02Epigenetics: heritable, reversible changes in gene activity without altering the DNA sequence
- 03DNA methyltransferases (writers) add methyl to cytosine → 5-methylcytosine at promoter CpG islands → gene silencing
- 04Promoter hypermethylation silences tumour suppressors (CDKN2A/p16, MLH1, BRCA1, APC)
- 05MLH1 silencing → mismatch-repair deficiency → microsatellite instability (MSI), which responds well to immunotherapy
- 06Histone modification (methylation, deacetylation) and non-coding RNA (lncRNA, miRNA; EPIC1-MYC)
- 07RTK → RAS → RAF → MEK → ERK (MAPK) proliferation pathway; ligand-independent activation
- 08PI3K → AKT pro-survival pathway (PTEN loss) and Wnt/APC/β-catenin (destruction complex)
Epigenetic silencing of MLH1 → microsatellite instability
- +1Epigenetics changes gene activity without altering the DNA sequence, and is reversible. DNA methyltransferases add a methyl group to cytosine at promoter CpG islands, producing 5-methylcytosine.
- +1Dense promoter hypermethylation closes the chromatin at that gene and silences its transcription — so a tumour-suppressor gene can be inactivated epigenetically, without any mutation.
- +1When the silenced gene is MLH1 (a mismatch-repair gene), the cell loses mismatch-repair function (MMR deficiency), so replication errors in short repeats go uncorrected → microsatellite instability (MSI).
- +1Therapeutic consequence: MSI tumours accumulate many mutations and therefore many neoantigens, making them paradoxically GOOD responders to immunotherapy (immune-checkpoint inhibitors).
Key terms
- Epigenetics
- Heritable, reversible changes in gene activity that do not alter the underlying DNA sequence, mediated by DNA methylation, histone modification and non-coding RNA.
- Promoter hypermethylation
- Dense addition of methyl groups to CpG islands in a gene's promoter, closing the chromatin and silencing transcription; a common way tumour-suppressor genes are inactivated without mutation.
- DNA methyltransferase (DNMT)
- An enzyme (a ‘writer’) that transfers a methyl group from SAM onto cytosine to form 5-methylcytosine, generally causing promoter silencing.
- Microsatellite instability (MSI)
- A hypermutable state caused by loss of DNA mismatch repair (e.g. MLH1 silencing); MSI tumours carry many neoantigens and respond well to immunotherapy.
- Viral oncogenesis
- Cancer driven by a virus; e.g. HPV integrates and expresses E6 (degrades p53) and E7 (degrades pRb), removing cell-cycle control.
- MAPK pathway
- The RTK → RAS → RAF → MEK → ERK proliferation cascade; oncogenic activation (RTK amplification/mutation or RAS locked in the GTP-bound state) makes it fire without an external ligand.
Cancer Gene Activation, Epigenetics & Driver Pathways FAQ
How can a tumour-suppressor gene be inactivated without a mutation?
Through epigenetic silencing: dense promoter CpG-island hypermethylation closes the chromatin and stops the gene being transcribed, so its protein is lost even though the DNA sequence is intact. CDKN2A, MLH1 and BRCA1 are silenced this way in various cancers.
How does HPV cause cancer?
HPV integrates into the host genome and expresses two oncoproteins: E6, which promotes degradation of p53, and E7, which degrades pRb. Losing both guardians removes cell-cycle control and drives proliferation — the mechanism to quote for cervical and oropharyngeal cancer.
How can the MAPK pathway fire without an external growth factor?
Either an RTK is amplified or mutated so it signals constitutively, or RAS is locked in its active GTP-bound state; either way RAF-MEK-ERK signals continuously without ligand. Drawing this ligand-independent activation is a flagship diagram question.
Can AI help me draw the driver pathways in AMED3001?
Yes — Sia can walk you through the MAPK, PI3K-AKT and Wnt/APC/β-catenin pathways node by node, check the direction of each arrow, and quiz you on where oncogenic activation occurs. It explains the method and checks your reasoning, not your graded work.
Exam move
Practise drawing the three driver pathways — RTK-RAS-RAF-MEK-ERK, PI3K-AKT and Wnt/APC/β-catenin — from memory, with the point of oncogenic activation marked, because ‘draw the pathway and show ligand-independent activation’ is a flagship question. Separately, drill the off-switch mechanisms: HPV E6/E7, promoter hypermethylation (MLH1 → MSI) and non-coding RNA, always stating direction correctly. Ask Sia to check arrow directions and re-explain any node; keep this warm for the final and confirm details on Canvas.
Working through Cancer Gene Activation, Epigenetics & Driver Pathways in AMED3001? Sia is AskSia’s AI Biology tutor — ask any AMED3001 Cancer Gene Activation, Epigenetics & Driver Pathways question and get a clear, step-by-step explanation grounded in how AMED3001 is taught and assessed. Read this chapter free, then take your hardest questions to Sia.
