Somatic Trp53 mutations differentially drive breast cancer and evolution of metastases

• DOI: 10.1038/s41467-018-06146-9
• Publication Date: 2018-09-21T12:52:29Z
• Authors: Yun Zhang; Shunbin Xiong; Bin Liu; Vinod Pant; Francis Celii; Gilda Chau; Ana C. Elizondo-F...; Peirong Yang; Mingjian James You; Adel K. El-Naggar; Nicholas E. Navin; Guillermina Lozano
• Keywords: 0303 health sciences; Carcinogenesis; Science; Q; Breast Neoplasms; Mammary Neoplasms, Animal; Article; 3. Good health; Mice, Inbred C57BL; Genetic Heterogeneity; 03 medical and health sciences; 616; Mutation; Animals; Humans; Female; Neoplasm Metastasis; Tumor Suppressor Protein p53; Alleles

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