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