Li Fraumeni

Question 1

What re the 3 criteria of Li Fraumeni Syndrome?

Answer 1

1. Proband with sarcoma diagnosed before 45
   AND
2. 1st degree relative with any cancer before 45
   AND
3. 1st or 2nd degree relative with any cancer under 45 or sarcoma at any age

Question 2

What are the 3 criteria for Li-Fraumeni Like Syndrome?

Answer 2

1. Proband with any childhood cancer or sarcoma, brain tumor or adrenal cortical tumor before 45
   AND
2. 1st or 2nd degree relative with a typical LFS cancer (sarcoma, breast, brain tumor, adrenal cortical tumor or leukemia) at any age
   AND
3. 1st or 2nd degree relative with any cancer under the age of 60 yrs

Question 3

What % of Li Fraumeni cancers have a p53 mutation?

Answer 3

70% (50% of all cancers)

Question 4

WHat is the 2 hit Knudson model for carcinogenesis in the context of LFS?

Answer 4

1st hit:
germline p53 point mutation

2nd hit:
carcinogenic event (i.e. amplification of HER2, lung cancer after radiation)

hits can be on different genes

Question 5

What are the common ways that cancer related “hits” occur?

Answer 5

point mutations
amplifications
deletions
epigenetic silencing by methylation
insertion of retrovirus containing oncogene

Question 6

What is the function of p53?

Answer 6

Cell cycle arrest
apoptosis
=>genetic stability

regulates transcription

• regulates transcription of damaged genes
• regulates micro RNA’s & protein coding genes

Target of conventional chemotherapy
-designed drugs can activate p53 without DNA damage