Distinguished Professor MD Anderson Cancer Center, Texas, United States
In this talk I will discuss our efforts to develop and apply single cell DNA sequencing technologies to study breast cancer invasion, metastasis and resistance to chemotherapy. Specifically we have developed methods such as Acoustic Cell Tagmentation (ACT) which can provide high-throughput single cell copy number profiling of hundreds of cells in parallel at single-molecule resolution. We have applied this approach to study copy number evolution in Triple-negative breast cancer which has revealed a ‘transient instability’ model of early copy number evolution, after the acquisition of TP53 mutations and genome doubling. We have also developed a computational approach called CopyKAT that can infer genomic copy number profiles from high-throughput single cell RNA data, which we have applied to reconstruct clonal substructure and evolution in breast, pancreatic and thyroid cancers. Collectively these studies and technologies provide new insights into the evolution of chromosome aberrations in human cancers.
