Biochemistry · Topic
Oncogenes and tumour suppressor genes !
Cancer arises from mutations that speed up division (oncogenes) or remove its brakes (tumour suppressors); this is the basic outline.
Updated 2026-11-01
Key facts
- Proto-oncogene: a normal gene that drives growth (factors, receptors, RAS, MYC); mutated or amplified it becomes an oncogene and acts with one copy (dominant in the cell).
- Tumour suppressor: brakes the cycle or repairs DNA (TP53, RB1, APC, BRCA1/2); both copies must be damaged: Knudson's two-hit hypothesis.
- Mutant RAS (KRAS) stays bound to GTP and always on; it is common in pancreas, colon and lung.
- p53, «guardian of the genome», halts the cycle in G1 (via p21), triggers repair or apoptosis; it is mutated in about half of cancers.
- RB brakes the G1→S transition by holding E2F; cyclin–CDK complexes phosphorylate it to release it.
In detail
- Normal signal: a growth factor activates its receptor tyrosine kinase, then RAS–RAF–MEK–ERK, and genes such as MYC switch on.
- Oncogene by point mutation (KRAS, BRAF V600E), amplification (HER2/ERBB2, N-MYC) or translocation (BCR-ABL in chronic myeloid leukaemia, MYC in Burkitt lymphoma).
- Lost suppressor: the first mutation can be inherited (familial retinoblastoma, Li-Fraumeni, BRCA) and the second happens in the tissue.
- Repair genes (MLH1, MSH2 in Lynch; BRCA1/2) are «caretaker» suppressors: their loss speeds up every other mutation.
- Cancer gathers several changes: self-sufficient growth signals, escape from brakes and apoptosis, immortality (telomerase), angiogenesis, invasion and reprogrammed metabolism (Warburg effect).
- Many targeted drugs hit specific oncogenes: imatinib (BCR-ABL), trastuzumab (HER2), BRAF and EGFR inhibitors.
Clinical notes
- Familial adenomatous polyposis (APC): hundreds of polyps and almost certain colon cancer without colectomy.
- BRCA1/2: high risk of breast and ovarian cancer; PARP inhibitors exploit the faulty repair.
- Li-Fraumeni (germline TP53): sarcomas, breast, brain and adrenal tumours at young ages.
- This is an outline: the molecular genetics of cancer is expanded in the molecular biology section.
Related conditions
- Colorectal cancer
- Breast cancer
- Ovarian cancer
- Lung cancer
- Pancreatic cancer
- Glioblastoma
- Hereditary paraganglioma and pheochromocytoma (SDH)
Related
- Warburg effect (aerobic glycolysis in cancer)
- Drugs acting on nucleotide metabolism
- Thymidylate synthase
- Dihydrofolate reductase (DHFR)
Test yourself
Think of the answer, then tap the question to see it.
Why is one mutated oncogene copy enough but two suppressor copies are needed?
The oncogene gains a function that dominates; the suppressor loses a brake, and the healthy copy keeps braking until it is lost too.
What does p53 do when it detects DNA damage?
It halts the cycle in G1 through p21, activates repair and, if the damage is large, apoptosis.
How is RAS activated as an oncogene?
A point mutation stops it hydrolysing GTP, so it stays switched on.
Which tumour suppressor gene is mutated in familial adenomatous polyposis?
APC, which normally tags β-catenin for degradation.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: TP53 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); KRAS gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); RB1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); APC gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); BRCA1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Li-Fraumeni syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Signaling by RAS mutants (Reactome, 2026); Cancer (World Health Organization, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.