Oncogenes and Tumour Suppressors: Why One Allele Is Sometimes Enough
Gain-of-function and loss-of-function lesions behave differently in a pedigree and in a tumour: a single altered allele can drive, while a suppressor usually needs both copies lost. This stop reads that difference out of inheritance patterns and tumour genotypes.
What a learner can do afterwards
- Predict dominance or recessiveness from the mechanism of a stated mutation
- Explain loss of heterozygosity and how it is detected in tumour sequence data
- Use a familial cancer pedigree to argue which class a gene belongs to
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You sort cancer genes by mechanism, not by name. Proto-oncogenes relay growth orders from the surface to the nucleus. A mutation locking one relay in the on position can drive the cell toward division without orders, though further changes are still needed. A single mutant copy can suffice because the stuck signal dominates. These activating changes are usually acquired in body cells. Rare inherited cases exist, so inheritance alone never names the class.
You treat suppressors the opposite way in the classic model. They build the brakes, so losing one copy usually leaves a working brake and the defect is recessive at the cellular level in the taught case. Trouble can start when the second copy is lost in some unlucky cell. Losing both removes one restraint; it does not guarantee cancer on its own. Some suppressors act by other means, so you keep this case as the model, not a universal rule.
You study eye tumours in one family. Children inherit one faulty copy of a brake gene, tumours appear early in both eyes, and each tumour shows loss at the marker, with allele tracking naming the lost copy as the healthy one in this family. That RB1 pattern pairs pedigree with genotype: inherited risk plus a tracked second hit in the tumour.
You read pedigrees with care. Early repeated tumours across generations show inherited risk, which often passes dominantly even when the cell level loss is recessive. But pedigree alone cannot settle the class: familial RET activation in MEN2 drives tumours from an inherited stuck relay. You need the tumour genotype with a matched normal check, plus the mechanism; family history alone never decides.
You treat repair gene defects as contributors. They raise the mutation rate, so harmful combinations can accumulate faster. They do not order growth themselves, and they do not touch each later step.
You detect the second hit by comparison. Normal tissue shows two variants at a marker, while the tumour shows one. That loss at the marker points to loss of heterozygosity there; deletion of a named copy needs allele level proof.
You call stuck relays oncogenes and lost brakes suppressors, you scope RB1 style pairs of pedigree plus genotype, and you confirm the second hit with tumour versus normal sequence.
Original readings written in-repo; academy video links retained with unknown terms.
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Where it sits
8 questions wait behind this lesson, each with its answer explained. Every answer feeds the sky: stars light as they are learned, and dim when it is time to come back.