Oncogenes are the accelerator, tumour suppressors the brakes
Expansion
| Oncogene | Tumour suppressor | |
|---|---|---|
| Normal role | Promotes growth (proto-oncogene) | Restrains growth, repairs DNA |
| Effect of mutation | Gain of function | Loss of function |
| Alleles needed | One (dominant at cell level) | Both (recessive at cell level) |
| Examples | RAS, MYC, HER2, BCR-ABL, EGFR | p53, RB, BRCA1/2, APC, VHL |
“Oncogenes are a stuck accelerator; tumour suppressors are failed brakes.”
Knudson’s two hit hypothesis explains inherited cancer syndromes: an individual inheriting one defective allele needs only one further somatic hit, so cancers occur earlier, more often and bilaterally. Sporadic cases need two independent hits and so occur later and singly. Retinoblastoma is the original example.
p53, the guardian of the genome, arrests the cell cycle at G1 for repair or triggers apoptosis. It is the most commonly mutated gene in human cancer, and its germline loss causes Li-Fraumeni syndrome.
A third class is the DNA repair genes, whose loss causes genomic instability: mismatch repair failure in Lynch syndrome, giving microsatellite instability, and BRCA in homologous recombination, which is what PARP inhibitors exploit.