Beyond these 23 mutations in likely cancer drivers, and reflecting the high degree of mutational heterogeneity observed in human breast cancers, 96 putative metastatic driver mutations that were not detected in primary tumors by UDS-UMI occurred in genes encoding components of signaling pathways with demonstrated roles in cancer (e.g., WNT1, FZD3, TSC1, JAK1, JAK2, JAK3, CCNE2, FBN1, INSR, LAMA1, NOTCH3, PIK3R2, PIK3CB, RELN) [7]. The gene discussed is NOTCH3; the disease is breast cancer.