Fig. 7: The diversity of claudin-low tumors reflects the impact of the cell-of-origin on the evolutionary process of breast tumorigenesis.

The malignant transformation of a normal MaSC leads to undifferentiated tumors with a low genomic instability and a low frequency of TP53 mutations. These features are characteristic of the CL1 subgroup. The activation of an EMT transdifferentiation process and the gain of mesenchymal features in a basal-like tumor promotes the development of a CL3 tumor with extensive genomic aberrations. EMT commitment in a luminal-like breast cancer leads gradually to a CL2 tumor with a moderate level of genomic aberrations.