Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing

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5 Scopus citations

Abstract

Single-cell DNA sequencing (scDNA-seq) methods are powerful tools for profiling mutations in cancer cells; however, most genomic regions sequenced in single cells are non-informative. To overcome this issue, we developed a multi-patient-targeted (MPT) scDNA-seq method. MPT involves first performing bulk exome sequencing across a cohort of cancer patients to identify somatic mutations, which are then pooled together to develop a single custom targeted panel for high-throughput scDNA-seq using a microfluidics platform. We applied MPT to profile 330 mutations across 23,500 cells from 5 patients with triple negative-breast cancer (TNBC), which showed that 3 tumors were monoclonal and 2 tumors were polyclonal. From these data, we reconstructed mutational lineages and identified early mutational and copy-number events, including early TP53 mutations that occurred in all five patients. Collectively, our data suggest that MPT can overcome a major technical obstacle for studying tumor evolution using scDNA-seq by profiling information-rich mutation sites.

Original languageEnglish (US)
Article number100215
JournalCell Genomics
Volume3
Issue number1
DOIs
StatePublished - Jan 11 2023

Keywords

  • breast cancer
  • intratumor heterogeneity
  • mutational evolution
  • single-cell genomics
  • triple-negative breast cancer

ASJC Scopus subject areas

  • Genetics
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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