Question

Li-Fraumeni Syndrome is a rare and inherited form of cancer. This syndrome runs in Tanner's family. Individuals with Li-Fraumeni Syndrome are born with a heterozygous mutation on the p53 gene (p53+/p53-) and have a greatly enhanced chance of getting cancer at a younger age. His paternal grandmother was diagnosed and died of breast cancer before she was 50 years old. There were other relatives on the paternal side that also had various kinds of cancer. His father, who is still living, was diagnosed with Li-Fraumeni Syndrome. When Tanner was 10 he had a bad headache, loss of appetite, and was very tired. After a few tests, he was diagnosed with a type of brain cancer known as glioblastoma. Unfortunately, Tanner died about 8 months later.

a) Using only what you've learned from this class, explain how a non-functional p53 mutation can lead to an accumulation of mutations and ultimately cancer. Make sure to include the following: E2F, Rb, P21, CDK, cell cycle,

b) Tanner has a sister. What is the probability that she will have Li-Fraumeni Syndrome?

c) His sister's parents have not yet tested her to determine if she has Li-Fraumeni Syndrome. What are one advantage of testing her and one disadvantage of testing her?

Answer 1

a) EF2, Rb and p53 are important regulators of cell cycle. p53 suppresses the cell proliferation mediated by the Rb-E2F pathway. So when p53 is mutated, this inhibition is lifted and the cell can undergo rapid proliferation. The loss of p53 function by mutation can disrupts its ability to produce p21. Without p21, there is no effective block on Cdk activation. So with a mutated or not functional p53, the G1 checkpoint fails and the cell proceeds directly from G1 to S irrespective of DNA damage. The rapid proliferation and cell division makes it a hallmark for cancer.  

b) Tanners father is heterozygous for the syndrome which is an autosomal dominant disease. So his Tanners paternal grandmother. But nothing is mentioned about this maternal inheritance so we have to assume that Tanners mother is recessive for the disease (does not have mutated p53 allele). Based on this info, the Punnett square will be as follows:

	A	a
a	Aa	aa
a	Aa	aa

So the chance of Tanner's sister to have the disease is 1/2.

c) One advantage of genetic testing is the management of the condition a person is diagnosed with. Proper medical care and counselling in neceasary. A disadvantage is that often increases the stress and anxiety in the person and disrupts the normalcy of their life.

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