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Somatic Trp53 mutations differentially drive breast cancer and evolution of metastases

Author

Listed:
  • Yun Zhang

    (University of Texas MD Anderson Cancer Center
    College of Pharmacy, Texas Southern University)

  • Shunbin Xiong

    (University of Texas MD Anderson Cancer Center)

  • Bin Liu

    (University of Texas MD Anderson Cancer Center)

  • Vinod Pant

    (University of Texas MD Anderson Cancer Center)

  • Francis Celii

    (University of Texas MD Anderson Cancer Center)

  • Gilda Chau

    (University of Texas MD Anderson Cancer Center)

  • Ana C. Elizondo-Fraire

    (University of Texas MD Anderson Cancer Center)

  • Peirong Yang

    (University of Texas MD Anderson Cancer Center)

  • Mingjian James You

    (University of Texas MD Anderson Cancer Center)

  • Adel K. El-Naggar

    (University of Texas MD Anderson Cancer Center)

  • Nicholas E. Navin

    (University of Texas MD Anderson Cancer Center)

  • Guillermina Lozano

    (University of Texas MD Anderson Cancer Center)

Abstract

TP53 mutations are the most frequent genetic alterations in breast cancer and are associated with more aggressive disease and worse overall survival. We have created two conditional mutant Trp53 alleles in the mouse that allow expression of Trp53R172H or Trp53R245W missense mutations in single cells surrounded by a normal stroma and immune system. Mice with Trp53 mutations in a few breast epithelial cells develop breast cancers with high similarity to human breast cancer including triple negative. p53R245W tumors are the most aggressive and exhibit metastases to lung and liver. Development of p53R172H breast tumors with some metastases requires additional hits. Sequencing of primary tumors and metastases shows p53R245W drives a parallel evolutionary pattern of metastases. These in vivo models most closely simulate the genesis of human breast cancer and will thus be invaluable in testing novel therapeutic options.

Suggested Citation

  • Yun Zhang & Shunbin Xiong & Bin Liu & Vinod Pant & Francis Celii & Gilda Chau & Ana C. Elizondo-Fraire & Peirong Yang & Mingjian James You & Adel K. El-Naggar & Nicholas E. Navin & Guillermina Lozano, 2018. "Somatic Trp53 mutations differentially drive breast cancer and evolution of metastases," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06146-9
    DOI: 10.1038/s41467-018-06146-9
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    Cited by:

    1. Fayang Ma & Kyle Laster & Zigang Dong, 2022. "The comparison of cancer gene mutation frequencies in Chinese and U.S. patient populations," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Ori Hassin & Nishanth Belugali Nataraj & Michal Shreberk-Shaked & Yael Aylon & Rona Yaeger & Giulia Fontemaggi & Saptaparna Mukherjee & Martino Maddalena & Adi Avioz & Ortal Iancu & Giuseppe Mallel & , 2022. "Different hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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