Makindo Medical Notes

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.