1. Patient VB
Li-Fraumeni Syndrome

2. Cancer Gene Detection Contributing Factors
Exposure to carcinogens such as those in the diet or environment
Genetics - Familial predispositions (hereditary patterns)

3. Somatic Mutation No direct genetic linkX
Mutations occur during lifetime
2 mutations for cancer to occur

4. Hereditary Germline Mutation
Germ cells - egg/sperm X
Dominant Inheritance
Pattern - 50% X
G - mutation, g - normal Gg X X
Inherits 1 mutation GG
A second somatic mutation
can result in cancer
Directly inherited - born with one mutation

5. Two-Hit Hypothesis
Two mutations required for uncontrolled cell division
Germline - one is inherited one more needed for cancer to occur
Somatic - two needed during lifetime

6. The Genes Proto-oncogenes - accelerator, promotes cell growth
Tumor suppressor genes - brakes, limits cell growth

7. Genetics - p53Gene Tumor suppressor gene
Produces a protein that limits cell growth and division
Found on chromosome 17
Normal protein binds to DNA that regulates transcription
Mutated fails to bind to DNA acts as an oncogene causing uncontrolled cell division

8. Li - Fraumeni Syndrome Discovered by two physicians, Li and Fraumeni
Usually includes a sarcoma (bone and blood cancers) patient
Two immediate relatives with other cancers before age 45
Multiple cancers in other family members

9. Patient’s Background Information
VB age 36 found a small mass in her breast
Mother had a mastectomy when in her late 30s
Visited physician diagnosed with breast cancer

10. Is VB’s Cancer Inherited? Li-Fraumeni?
First step is to establish a pedigree
Second step - p53 Diagnostic Test

11. Step 1 - Pedigree
Complete the pedigree with the information you are given

12. Initial Diagnosis?
Li-Fraumeni?

13. Step 2 - DNA Analysis Blood Sample Tumor Tissue Sample
Normal Breast Tissue Sample

14. DNA p53 Gene Analysis
Step 1 - DNA digested with a restriction enzyme that recognizes the mutant sequence (enzyme cleaves the mutant p53 sequence into 2 smaller sequences)
Step 2 - DNA sequence is amplified using Polymerase Chain Reaction (PCR)
Step 3 - Samples along with controls are run on a gel

15. YOUR JOB IS TO: Inject the samples into a gel Run the gel
Determine if Li -Fraumeni syndrome is in this family