Patient VB Li-Fraumeni Syndrome

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

Somatic Mutation No direct genetic link X Mutations occur during lifetime 2 mutations for cancer to occur

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

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

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

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

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

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

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

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

Initial Diagnosis? Li-Fraumeni?

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

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

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