SPEC 3.8.2.3 - GENE EXPRESSION & CANCER
Gene Expression & Cancer
Tumour Suppressor Genes, Oncogenes, Abnormal Methylation & Breast Cancer
What is Cancer?
Cancer arises when the normal controls over the cell cycle break down, resulting in uncontrolled cell division. This produces a mass of abnormally dividing cells called a tumour.
Key Definition
A tumour is an abnormal mass of cells resulting from uncontrolled cell division. Tumours can be benign or malignant.
Cancer typically requires multiple mutations accumulating in the same cell over time. Two key gene types are involved in most cancers:
Proto-oncogenes
Normally promote cell growth and division. When mutated they become oncogenes — driving uncontrolled division.
Tumour Suppressor Genes
Normally inhibit cell division. When both alleles are inactivated, the braking system is lost.
Examiner Tip
Cancer is a disease of gene expression — it can arise from DNA base sequence mutations AND from epigenetic changes that alter whether genes are switched on or off.
Benign vs Malignant Tumours
✓ Benign Tumour
Localised — stays in one place
Surrounded by a capsule
Does not invade surrounding tissue
Does not metastasise
Generally less life-threatening
✗ Malignant Tumour
Invasive — spreads into surrounding tissue
No surrounding capsule
Metastasises — cells travel via blood or lymph to form secondary tumours
Life-threatening; harder to treat
Key Definition
Metastasis — the spread of malignant cancer cells from a primary tumour to distant sites in the body via the bloodstream or lymphatic system, forming secondary tumours.
Proto-Oncogenes & Oncogenes
Key Definitions
Proto-oncogene: A normal gene coding for proteins that promote cell growth and division — essential for normal development and repair.
Oncogene: A mutated proto-oncogene. Produces growth-promoting signals continuously, even without normal growth signals → uncontrolled cell division.
When a proto-oncogene is mutated into an oncogene:
1
The gene is permanently switched on (or its protein product is overactive)
2
Growth-promoting proteins are produced continuously
3
The cell divides uncontrollably → tumour formation
Analogy
An oncogene is like an accelerator pedal stuck down — the cell is forced to keep dividing regardless of signals to stop.
Tumour Suppressor Genes
Key Definition
Tumour suppressor gene: A gene that normally inhibits cell division by producing proteins that slow or stop the cell cycle. If both copies (alleles) are inactivated, the braking system is lost.
The Two-Hit Hypothesis
Each cell has two alleles of every tumour suppressor gene. Both must be inactivated for cell cycle control to be lost:1Hit 1: First allele inactivated — may be an inherited mutation or a somatic (acquired) mutation2Hit 2: Second allele inactivated by a further somatic mutation → no functional inhibitory protein → cell division unchecked
Analogy
Tumour suppressor gene = brakes on a car. Oncogene = accelerator stuck down. Cancer arises when the brakes also fail.
Multiple Mutations & Cancer
Cancer typically requires several mutations accumulating in the same cell. A single mutation is rarely sufficient because cell division has multiple independent controls:
Why Multiple Mutations?
For uncontrolled division to occur, mutations must overcome both types of control in the same cell:
Oncogene activation — mutation causes continuous growth-promoting signals
Tumour suppressor inactivation — both alleles lost → no inhibition of division
Because these are separate controls, mutations in both types of gene are typically needed before uncontrolled division results.
Key Principle
Mutations accumulate over a lifetime due to: spontaneous replication errors, mutagenic agents (UV, chemicals, ionising radiation), or viral infection. This explains why cancer risk increases with age.
Examiner Tip
AQA may ask you to evaluate evidence correlating genetic and environmental factors with cancer. Be ready to discuss both inherited predisposition and environmental mutagens.
Abnormal Methylation in Cancer
Cancer can develop through epigenetic changes — without any change to the DNA base sequence. Abnormal methylation patterns can silence tumour suppressor genes or activate oncogenes.
↑ Hypermethylation of TSG Promoter
Promoter region heavily methylated → gene silenced → no tumour suppressor protein produced → cell division goes unchecked
↓ Hypomethylation of Oncogene Promoter
Less methylation than normal → oncogene overexpressed → continuous growth-promoting signals → uncontrolled division
Why This Matters
Epigenetic changes are heritable to daughter cells — passed on at mitosis. Crucially, unlike DNA base sequence mutations, epigenetic changes are potentially reversible, making them attractive therapeutic targets.
Don't Confuse
Hypermethylation silences tumour suppressors (→ promotes cancer). Hypomethylation overactivates oncogenes (→ promotes cancer). Both abnormal changes promote cancer development.
Oestrogen & Breast Cancer
Oestrogen is a steroid hormone that acts as a transcription factor, linking Topic 8.03 (gene regulation) directly to cancer risk.
1
Oestrogen is lipid-soluble — diffuses across the cell-surface membrane and binds to its intracellular receptor
2
The hormone-receptor complex moves into the nucleus and acts as a transcription factor, binding to specific DNA regulatory sequences
3
This activates transcription of genes that promote cell division in breast tissue
4
Elevated oestrogen concentrations → increased rate of cell division → greater chance of mutations accumulating → increased breast cancer risk
Treatment Application
Drugs such as tamoxifen block oestrogen receptors in breast tissue — the hormone-receptor complex cannot form, so transcription of cell division genes is not activated. This is an example of using knowledge of gene expression to treat cancer.
Evaluating Evidence: Genetic vs Environmental
AQA expects you to evaluate evidence correlating genetic and environmental factors with cancer risk.
Genetic Risk FactorsEnvironmental Risk Factors
Inherited mutations in oncogenes or tumour suppressor genesMutagenic agents: UV radiation, ionising radiation, chemical carcinogens (e.g. tobacco smoke)
Epigenetic changes heritable to daughter cells at mitosisDiet, lifestyle, viral infections (e.g. HPV → cervical cancer)
Family history suggests inherited predispositionEnvironmental exposures increase somatic mutation rate over lifetime
Evaluation Framework
When evaluating data: (1) Is there a correlation? (2) Is it causal or could confounding variables explain it? (3) Is the sample size adequate? (4) Have alternative explanations been ruled out? (5) Correlation ≠ causation.
Prevention, Treatment & Cure
AQA asks you to interpret information about how knowledge of oncogenes and tumour suppressor genes can be applied in practice.
ApplicationHow Knowledge is AppliedExample
PreventionGenetic screening for inherited mutations → identify high-risk individualsBRCA1/2 testing → increased surveillance
TreatmentBlock specific molecular pathways disrupted in cancerTamoxifen blocks oestrogen receptor
TreatmentEpigenetic drugs — reverse abnormal methylation patternsDemethylating agents to reactivate silenced tumour suppressor genes
Cure (experimental)Gene therapy — introduce functional tumour suppressor gene into cancer cellsp53 gene therapy to restore cell cycle control
Key Principle
The potential reversibility of epigenetic changes (unlike DNA base sequence mutations) makes epigenome-targeting drugs particularly promising for cancer treatment.
Summary
Tumour Types
Benign: Localised, encapsulated, does not metastasise
Malignant: Invasive, metastasises via blood/lymph to form secondary tumours
Gene Types in Cancer
Proto-oncogene → oncogene: Mutation → permanent growth signals → uncontrolled division (accelerator stuck)
Tumour suppressor gene: Both alleles must be inactivated (two-hit) → no braking → division unchecked (brakes fail)
Abnormal Methylation
Hypermethylation of TSG promoter: Silences gene → no inhibitory protein → cancer promoted
Hypomethylation of oncogene promoter: Gene overexpressed → excess growth signals → cancer promoted
Oestrogen & Breast Cancer
High [oestrogen] → oestrogen-receptor complex acts as transcription factor → activates transcription of cell division genes → increased division rate → more mutations → elevated breast cancer risk
Tamoxifen blocks oestrogen receptor → prevents activation of cell division genes
Quick-Check Practice
Q1. Distinguish between a benign and a malignant tumour. [2 marks]
A benign tumour is localised / does not spread to other tissues / does not metastasise (1). A malignant tumour is invasive and can metastasise via blood or lymph to form secondary tumours at distant sites (1).
Q2. Explain how abnormal methylation of a tumour suppressor gene can contribute to cancer development. [3 marks]
Abnormal hypermethylation of the promoter region of the tumour suppressor gene (1); prevents transcription / silences the gene (1); so no tumour suppressor protein is produced and cell division is no longer inhibited / uncontrolled division occurs (1).
Q3. Explain how elevated oestrogen concentrations increase the risk of breast cancer. [3 marks]
Oestrogen binds to its intracellular receptor; the hormone-receptor complex acts as a transcription factor (1); activating transcription of genes that promote cell division in breast tissue (1); elevated oestrogen → increased rate of cell division → greater chance of mutations accumulating / increased cancer risk (1).
Q4. State the two-hit hypothesis for tumour suppressor genes. [2 marks]
Both alleles / copies of the tumour suppressor gene must be inactivated (1); before the inhibitory effect on cell division is lost and uncontrolled division can occur (1).
Next: What is Cancer?