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A continuum model for tumour suppression

Author

Listed:
  • Alice H. Berger

    (Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Alfred G. Knudson

    (Fox Chase Cancer Center)

  • Pier Paolo Pandolfi

    (Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School)

Abstract

Tumour suppression modelled The 'two-hit' hypothesis of tumorigenesis, originally proposed in 1971 by Alfred Knudson using retinoblastoma as a model, explained the role of recessive tumour suppressor genes (TSGs) in dominantly inherited cancer-susceptibility syndromes, in which tumorigenesis was later shown to require two mutations, one in each copy of a single tumour suppressor gene. Four decades later, it is clear that even partial inactivation of tumour suppressors can critically contribute to tumorigenesis. This Review by Alice Berger, Alfred Knudson and Pier Paolo Pandolfi proposes a continuum model of TSG function to explain the full range of TSG mutations found in cancer.

Suggested Citation

  • Alice H. Berger & Alfred G. Knudson & Pier Paolo Pandolfi, 2011. "A continuum model for tumour suppression," Nature, Nature, vol. 476(7359), pages 163-169, August.
    • Handle: RePEc:nat:nature:v:476:y:2011:i:7359:d:10.1038_nature10275
    DOI: 10.1038/nature10275
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    Cited by:

    1. Solip Park & Fran Supek & Ben Lehner, 2021. "Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    2. Avantika Ghosh & Marisa Riester & Jagriti Pal & Kadri-Ann Lainde & Carla Tangermann & Angela Wanninger & Ursula K. Dueren & Sonam Dhamija & Sven Diederichs, 2024. "Suppressive cancer nonstop extension mutations increase C-terminal hydrophobicity and disrupt evolutionarily conserved amino acid patterns," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Janine H. Ree & Karthik B. Jeganathan & Raul O. Fierro Velasco & Cheng Zhang & Ismail Can & Masakazu Hamada & Hu Li & Darren J. Baker & Jan M. Deursen, 2023. "Hyperphosphorylated PTEN exerts oncogenic properties," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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