Faculty, Staff and Student Publications

Publication Date

8-31-2023

Journal

Cell

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.

Keywords

Female, Humans, Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Intraductal, Noninfiltrating, Disease Progression, Genomics, Single-Cell Gene Expression Analysis, Cell Line, Tumor

DOI

10.1016/j.cell.2023.07.024

PMID

37586362

PMCID

PMC11831769

PubMedCentral® Posted Date

8-31-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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