Li Fraumeni Vignette Flashcards
1
Q
Clinical Criteria of LFS
A
Sarcoma before 45
First degree relative with cancer before 45
First or second degree relative with any cancer before 45 or sarcoma.
2
Q
Knudsen 2 Hit Hypothesis
A
Multiple hits needed to develop cancer. Inheriting one poor gene copy is 1 hit, 2nd hit is loss of only good copy which leads to cancer.
3
Q
p53 and DNA damage
A
Regulates expression of anti-cancer genes. Stabilized by ATM, ATR, Chk1&2. Inhibited by ubiquitin ligase MDM2 which target p53 for degradation..
Most mutations occur in DNA binding domain.
4
Q
What causes LFS?
A
Inherited cancer susceptibility disease usually caused by p53 mutation.
5
Q
Causes of LFS? (2)
A
70% p53 mutation
5-10% other high penetrance heritable mutations
6
Q
How to test for LFS
A
sequence p53 gene
