USMLE Why is Li-Fraumeni syndrome autosomal dominant?

[DingDongD]

I know Li-Fraumeni syndrome is mutation of p53, which is a tumor suppressor. I assumed that tumor suppressor follow two-hit hypothesis. So, wouldn't Li-Fraumeni syndrome be considered autosomal recessive since there has to be loss of heterogeneity? Thanks!

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[FindersFee5]

Most of the tumor suppressor disorders are considered autosomal dominant - it's kinda strange initially but makes sense when you think about it.

Let's take Li-Fraumeni as an example. When you have one mutated p53, you have Li-Fraumeni syndrome. Then it's only a matter of time until you get another p53 mutation from every day wear and tear on your genes and develop one of the archetypal cancers. You had the syndrome all along, and the inevitable cancers are a symptom of that syndrome.

Also, I'm pretty sure that homozygous p53 mutations (as with most of the big cell cycle regulators) are incompatible with life.

 

[Aerus]

Like FindersFee5 said, it's the SUSCEPTIBILITY that's autosomal dominant. You only need one copy of the mutation to have that susceptibility.