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
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons