Breast tumours maintain a reservoir of subclonal diversity during expansion.
Darlan C MinussiMichael D NicholsonHanghui YeAlexander DavisKaile WangToby M BakerMaxime TarabichiEmi SeiHaowei DuMashiat RabbaniCheng PengMin HuShanshan BaiYu-Wei LinAislyn SchalckAsha MultaniJin MaThomas O McDonaldAnna CasasentAngelica BarreraHui ChenBora LimBanu ArunFunda Meric-BernstamPeter Van LooFranziska MichorNicholas E NavinPublished in: Nature (2021)
Our knowledge of copy number evolution during the expansion of primary breast tumours is limited1,2. 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 tumour cells rediversify their genomes and do not retain isogenic properties. These data show that triple-negative breast cancers continue to evolve chromosome aberrations and maintain a reservoir of subclonal diversity during primary tumour growth.
Keyphrases
- copy number
- mitochondrial dna
- genome wide
- single molecule
- single cell
- induced apoptosis
- dna methylation
- cell cycle arrest
- endothelial cells
- healthcare
- living cells
- cell death
- rna seq
- oxidative stress
- gene expression
- signaling pathway
- circulating tumor
- high throughput
- cell proliferation
- young adults
- artificial intelligence
- deep learning
- cell free