Metastatic Competence Can Emerge with Selection of Preexisting Oncogenic Alleles without a Need of New Mutations.

摘要: Several experimental models faithfully recapitulate many important facets of human metastatic disease. Here we have performed whole exome sequencing in five widely used metastasis that were independently derived through vivo selection from heterogeneous cancer cell lines. In addition to providing an characterization these model systems, our study examines the genetic evolution phenotypes. We found selected highly populations showed little divergence corresponding parental population. However, variations preexisted populations, including well-established oncogenic mutations KRASG13D and BRAFG464V, was associated with increased capability. Conversely, expression wild-type BRAF allele cells inhibited outgrowth as well tumor initiation mice. Our findings establish competence can arise without need for acquisition additional mutations, such benefit further tumor-initiating seed primary tumorigenesis.