Neoplasia Theory

Two Hit Theory

Associated with 2 cellular oncogenes
- 1. Proto-oncogenes
  - Activated
- 2. Suppressor Genes
  - Lost
Proto-oncogenes become active oncogenes after alterations such as
- Point mutations
- Re-arrangement
- Gene application
Tumour Suppressor genes play an opposite role in tumour development
- Inactivation or loss results in a tumour
Need both situations to occur
- Includes p53 & RB1
  - p53
    - Associated with soft tissue sarcoma
  - RB1
    - Retinoblastoma Suppressor Gene
    - Chr13
    - 40% of soft tissue sarcoma have lost single copy of it
    - ? Congenitally only 1 copy, then other stops working
Some patients have genetic predisposition to neoplasia secondary to abnormal suppressor gene