Archival single-cell genomics reveals persistent subclones during DCIS progression.
Cell
; 186(18): 3968-3982.e15, 2023 08 31.
Article
em En
| MEDLINE
| ID: mdl-37586362
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Carcinoma Ductal de Mama
/
Carcinoma Intraductal não Infiltrante
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos