Breast tumours maintain a reservoir of subclonal diversity during expansion.

ABSTRACT: Our knowledge of copy number evolution during the expansion of primary breast tumours is limited^1,2. Here, to investigate this process, we developed a single-cell, single-molecule DNA-sequencing method and performed copy number analysis of 16,178 single cells from 8 human triple-negative breast cancers and 4 cell lines. The results show that breast tumours and cell lines comprise a large milieu of subclones (7-22) that are organized into a few (3-5) major superclones. Evolutionary analysis suggests that after clonal TP53 mutations, multiple loss-of-heterozygosity events and genome doubling, there was a period of transient genomic instability followed by ongoing copy number evolution during the primary tumour expansion. By subcloning single daughter cells in culture, we show that

SUBMITTER: Minussi DC 

PROVIDER: S-EPMC8049101 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature