Cell · 2023
Archival single-cell genomics reveals persistent subclones during DCIS progression.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Wang Kaile, Kumar Tapsi, Wang Junke, Minussi Darlan Conterno, Sei Emi, Li Jianzhuo, Tran Tuan M, Thennavan Aatish, Hu Min, Casasent Anna K, Xiao Zhenna, Bai Shanshan, Yang Lei, King Lorraine M, Shah Vandna, Kristel Petra, van der Borden Carolien L, Marks Jeffrey R, Zhao Yuehui, Zurita Amado J, Aparicio Ana, Chapin Brian, Ye Jie, Zhang Jianjun, Gibbons Don L, Grand Challenge PRECISION Consortium, Sawyer Ellinor, Thompson Alastair M, Futreal Andrew, Hwang E Shelley, Wesseling Jelle, Lips Esther H, Navin Nicholas E
Аннотация
Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary DCIS had already undergone whole-genome doubling and clonal diversification and that they shared genomic lineages with persistent subclones in the recurrences. Evolutionary analysis suggests that most DCIS cases in our cohort underwent an evolutionary bottleneck, and further identified chromosome aberrations in the persistent subclones that were associated with recurrence.