Abstract

Abstract I will discuss our efforts to develop and apply single cell DNA sequencing technologies to study breast cancer progression and evolution. We have developed a method called 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 toolkit called CopyKit to analyze single cell DNA sequencing data, and applied it to study metastasis in breast and colon cancer, as well as the spatial organization of subclones in metastatic tumors. Collectively these studies and tools provide new insights into the evolution of chromosome aberrations in human tumors. Citation Format: Nicholas Navin. Decoding breast cancer evolution with single cell genomics [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA025.

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