Archival single-cell genomics reveals persistent subclones during DCIS progression.

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2023-08-31 Epub Date: 2023-08-15 DOI:10.1016/j.cell.2023.07.024

Kaile Wang, Tapsi Kumar, Junke Wang, Darlan Conterno Minussi, Emi Sei, Jianzhuo Li, Tuan M Tran, Aatish Thennavan, Min Hu, Anna K Casasent, Zhenna Xiao, Shanshan Bai, Lei Yang, Lorraine M King, Vandna Shah, Petra Kristel, Carolien L van der Borden, Jeffrey R Marks, Yuehui Zhao, Amado J Zurita, Ana Aparicio, Brian Chapin, Jie Ye, Jianjun Zhang, Don L Gibbons, Ellinor Sawyer, Alastair M Thompson, Andrew Futreal, E Shelley Hwang, Jelle Wesseling, Esther H Lips, Nicholas E Navin

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引用次数: 2

Abstract

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.

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档案单细胞基因组学揭示了DCIS进展过程中持续存在的亚克隆。

原位导管癌（DCIS）是癌症侵袭性病变的常见前兆。我们对其基因组进展为复发性疾病的了解仍然很差，部分原因是与福尔马林固定石蜡包埋（FFPE）材料的基因组分析相关的挑战。在这里，我们开发了Arc well，这是一种与FFPE材料兼容的高通量单细胞DNA测序方法。我们通过对40330个来自细胞系、冷冻组织的单细胞和27个来自乳腺、肺和前列腺肿瘤的FFPE样本进行分析来验证我们的方法，这些样本保存了3-31年。对10名匹配DCIS和2-16年后复发的癌症患者的分析表明，许多原发性DCIS已经经历了全基因组加倍和克隆多样化，并且在复发中他们与持续的亚克隆共享基因组谱系。进化分析表明，我们队列中的大多数DCIS病例都经历了进化瓶颈，并进一步确定了与复发相关的持续亚克隆中的染色体畸变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.