A study published in Nature (2014) reveals clonal evolution in breast cancer using single nucleus genome sequencing. Researchers developed a method called Nuc-Seq, which uses G2/M nuclei to achieve high coverage and low error rates. This method was applied to analyze an estrogen-receptor positive (ER+) breast cancer and a triple-negative ductal carcinoma (TNBC). The study found that aneuploid rearrangements occurred early in tumor evolution and remained stable, while point mutations evolved gradually, generating extensive clonal diversity. Many mutations were present at low frequencies (<10%) in the tumor mass. Mathematical modeling showed that TNBC cells had a 13.3X higher mutation rate than ER+ cells. The study also identified subclonal and de novo mutations, which may play a role in tumor evolution and chemoresistance. The findings have implications for cancer diagnosis, treatment, and understanding of tumor heterogeneity. The study highlights the importance of single-cell sequencing in understanding clonal diversity and mutation rates in breast cancer. The research provides insights into the mechanisms of clonal evolution and the role of mutations in tumor progression. The study also emphasizes the need for further research into the genetic diversity of breast cancer and its implications for treatment. The results suggest that many mutations are likely to be real biological variants that occur at low frequencies in the tumor mass. The study underscores the significance of single-cell sequencing in uncovering the genetic complexity of breast cancer and its potential applications in cancer research and clinical practice.A study published in Nature (2014) reveals clonal evolution in breast cancer using single nucleus genome sequencing. Researchers developed a method called Nuc-Seq, which uses G2/M nuclei to achieve high coverage and low error rates. This method was applied to analyze an estrogen-receptor positive (ER+) breast cancer and a triple-negative ductal carcinoma (TNBC). The study found that aneuploid rearrangements occurred early in tumor evolution and remained stable, while point mutations evolved gradually, generating extensive clonal diversity. Many mutations were present at low frequencies (<10%) in the tumor mass. Mathematical modeling showed that TNBC cells had a 13.3X higher mutation rate than ER+ cells. The study also identified subclonal and de novo mutations, which may play a role in tumor evolution and chemoresistance. The findings have implications for cancer diagnosis, treatment, and understanding of tumor heterogeneity. The study highlights the importance of single-cell sequencing in understanding clonal diversity and mutation rates in breast cancer. The research provides insights into the mechanisms of clonal evolution and the role of mutations in tumor progression. The study also emphasizes the need for further research into the genetic diversity of breast cancer and its implications for treatment. The results suggest that many mutations are likely to be real biological variants that occur at low frequencies in the tumor mass. The study underscores the significance of single-cell sequencing in uncovering the genetic complexity of breast cancer and its potential applications in cancer research and clinical practice.