Somatic Trp53R245W mutation drives parallel evolutionary pattern of breast cancer metastases

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 a novel conditional mutant Trp53 allele in the mouse that allows expression of Trp53R245W missense mutation in single cells surrounded by a normal stroma and immune system. Mice with Trp53R245W mutations in a few breast epithelial cells developed breast cancers with high similarity to human breast cancer, and exhibited metastases to lung and liver. Sequencing of primary tumors and metastases showed Trp53R245W drives parallel evolutionary pattern of metastases.