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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Zhang Y,Xiong S,Liu B,Pant V,Celii F,Chau G,Elizondo-Fraire AC,Yang P,You MJ,El-Naggar AK,Navin NE,Lozano Gdoi
10.1038/s41467-018-06146-9subject
Has Abstractpub_date
2018-09-27 00:00:00pages
3953issue
1issn
2041-1723pii
10.1038/s41467-018-06146-9journal_volume
9pub_type
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