The study investigates the clonal and mutational evolution spectrum of primary triple-negative breast cancers (TNBCs), a tumor type characterized by the lack of estrogen receptor, progesterone receptor, and ERBB2 gene amplification. The research analyzed 104 TNBC cases using high-throughput RNA sequencing and deep re-sequencing to determine the relative abundance of clonal frequencies. Key findings include: 1. **Genomic Evolution Spectrum**: TNBCs exhibit a wide range of genomic evolution, with some cases having only a few coding somatic aberrations in a few pathways, while others contain hundreds of coding somatic mutations. 2. **Mutation Expression**: Only about 36% of mutations are expressed, as revealed by RNA sequencing. 3. **Clonal Frequencies**: The study determined the relative abundance of clonal frequencies among cases, finding that basal TNBCs show more variation in clonal frequencies compared to non-basal TNBCs. 4. **Driver Genes and Pathways**: p53, PIK3CA, and PTEN mutations are clonally dominant, but their clonal frequencies are not always founder status. Mutations in cytoskeletal, cell shape, and motility proteins occur at lower clonal frequencies, suggesting they may be acquired later in tumor progression. 5. **Clonal Heterogeneity**: TNBCs display a continuum of clonal heterogeneity, with some cases showing low-clonality cancers and others exhibiting extensive clonal evolution at diagnosis. 6. **Clonal Analysis**: Using a Dirichlet process model, the study estimated clonal frequencies and mutation genotypes, revealing a wide spectrum of clonal frequency modes among cases. The findings highlight the need to understand the individual clonal genotypes of TNBCs to improve therapeutic approaches.The study investigates the clonal and mutational evolution spectrum of primary triple-negative breast cancers (TNBCs), a tumor type characterized by the lack of estrogen receptor, progesterone receptor, and ERBB2 gene amplification. The research analyzed 104 TNBC cases using high-throughput RNA sequencing and deep re-sequencing to determine the relative abundance of clonal frequencies. Key findings include: 1. **Genomic Evolution Spectrum**: TNBCs exhibit a wide range of genomic evolution, with some cases having only a few coding somatic aberrations in a few pathways, while others contain hundreds of coding somatic mutations. 2. **Mutation Expression**: Only about 36% of mutations are expressed, as revealed by RNA sequencing. 3. **Clonal Frequencies**: The study determined the relative abundance of clonal frequencies among cases, finding that basal TNBCs show more variation in clonal frequencies compared to non-basal TNBCs. 4. **Driver Genes and Pathways**: p53, PIK3CA, and PTEN mutations are clonally dominant, but their clonal frequencies are not always founder status. Mutations in cytoskeletal, cell shape, and motility proteins occur at lower clonal frequencies, suggesting they may be acquired later in tumor progression. 5. **Clonal Heterogeneity**: TNBCs display a continuum of clonal heterogeneity, with some cases showing low-clonality cancers and others exhibiting extensive clonal evolution at diagnosis. 6. **Clonal Analysis**: Using a Dirichlet process model, the study estimated clonal frequencies and mutation genotypes, revealing a wide spectrum of clonal frequency modes among cases. The findings highlight the need to understand the individual clonal genotypes of TNBCs to improve therapeutic approaches.