Tumour Suppressor Genes
Tumour suppressor genes are essential for controlling cell growth and division, acting as the body’s "brakes" against uncontrolled proliferation 🚦.
When mutated or inactivated, these safeguards fail, leading to tumour development and cancer.
📌 Key Concepts
- Functions 🛡️:
- Regulate cell cycle progression ⏳
- Repair DNA damage 🧪
- Induce apoptosis (programmed cell death) 💀
- Maintain genomic stability 🔬
- Mechanisms of Action ⚙️:
- Gatekeepers 🔑 – Directly regulate checkpoints/apoptosis (e.g. p53).
- Caretakers 🧹 – Preserve genomic integrity via DNA repair (e.g. BRCA1/2).
⭐ Key Tumour Suppressor Genes
- p53 🧾 – "Guardian of the genome"
- DNA repair activation after damage.
- Triggers apoptosis if DNA cannot be fixed.
- Mutated in ~50% of all cancers.
- RB (Retinoblastoma) 👁️
- Controls G1 → S checkpoint.
- Prevents premature cell division.
- Loss leads to retinoblastoma & other cancers.
- BRCA1 / BRCA2 🎀
- DNA repair by homologous recombination.
- Mutations → ↑ risk of breast, ovarian, prostate cancers.
- PTEN ⚡
- Inhibits PI3K/AKT pathway (cell growth signal).
- Mutations linked to breast, prostate, endometrial cancers.
- APC 🌿
- Regulates Wnt pathway (growth & differentiation).
- Mutations → Familial Adenomatous Polyposis (FAP), colorectal cancer.
🧨 Mechanisms of Inactivation
- Mutations – Point mutations, insertions, deletions → loss of function.
- Epigenetic Modifications – DNA methylation/histone changes silence genes.
- Loss of Heterozygosity (LOH) – Loss of the normal allele when the other is already mutated.
🏥 Clinical Relevance
- Diagnosis 🔍: Genetic testing for hereditary cancer syndromes (e.g. BRCA1/2).
- Prognosis 📉: p53 mutations often linked to worse outcomes.
- Therapy 🎯: Targeted treatments – e.g. PARP inhibitors in BRCA-mutated cancers.
🧾 Cancer Syndromes & Gene Links
- Li-Fraumeni Syndrome 🧬 – p53 mutation → high risk of sarcomas, breast, brain tumours.
- Retinoblastoma 👁️ – RB gene mutation → childhood retinal tumours.
- Familial Adenomatous Polyposis (FAP) 🌿 – APC mutation → hundreds of colonic polyps, inevitable colorectal cancer if untreated.
- Cowden Syndrome 🌸 – PTEN mutation → benign hamartomas & ↑ breast, thyroid, endometrial cancers.
📝 Summary
Tumour suppressor genes are the body’s natural defence against cancer 🚦.
When inactivated by mutation, methylation, or LOH, cells escape normal controls, leading to malignancy.
Understanding their role is critical for diagnosis, prognosis, and modern targeted therapies.
