Somatic Trp53 mutations differentially drive breast cancer and evolution of metastases

Authors

Yun Zhang, University of Texas MD Anderson Cancer Center
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

Document Type

Article

Publication Date

12-1-2018

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.

Recommended Citation

Zhang, Yun; Xiong, Shunbin; Liu, Bin; Pant, Vinod; Celii, Francis; Chau, Gilda; Elizondo-Fraire, Ana C.; Yang, Peirong; You, Mingjian James; El-Naggar, Adel K.; Navin, Nicholas E.; and Lozano, Guillermina, "Somatic Trp53 mutations differentially drive breast cancer and evolution of metastases" (2018). Faculty Publications. 140.
https://digitalscholarship.tsu.edu/facpubs/140