Gain of function mutations (proto-oncogenes)

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Created by
Mak Weng Huen Hailey (Tmjc)

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Cards (15)

  • results in
    • excessive amount of proteins due to increased transcription -> leads to increase in translation
    • hyperactive proteins due to changes to 3D conformation of the protein that confer abnormally high activity
  • What?
    when a proto-oncogene is mutated to become an oncogene
    -> mutated allele is more active than the normal allele
  • Proto-oncogene undergoes genetic change -> increase in amount of proto-oncogene's protein product or activity of each protein molecule -> over-stimulation of the cell cycle/uncontrolled cell division -> cancer
  • Most oncogenes are dominant alleles
  • Mutation in one of the 2 proto-oncogene alleles would be sufficient in producing excess proteins or hyperactive protein to induce cancer
  • Genetic changes that convert a proto-oncogene to an oncogene:
    1. Point mutations in the proto-oncogene itself OR a control element
    2. Amplification of a proto-oncogene
    3. Chromosomal translocation within the genome
  • (1)Point mutations in proto-oncogene itself or a control element
    • a point mutation in the proto-oncogene -> results in hyperactive protein than the normal protein due to changes in its 3D conformation
    • occurs in the promoter or enhancer that controls a proto-oncogene -> makes altered promoter or enhancer binds to transcription factors more strongly leading to an increase in expression of the proto-oncogene
    • e.g. point mutation of Ras gene in colorectal cancer
  • (2) Amplification of a proto-oncogene
    • increases the number of copies of the proto-oncogene in the cell through repeated gene duplication -> leads to excessive amount of the encoded protein in the cell
  • (3) Chromosomal translocation within the genome
    • translocation involves a region of a chromosome breaking off and rejoining either to same chromosome or another non-homologous chromosome
    • a proto-oncogene may be translocated downstream of an active promoter or other conrol elements, -> increased rate of transcription and translation of the protein that stimulates cell division