Faculty, Staff and Student Publications
Publication Date
1-11-2023
Journal
Cell Genomics
DOI
10.1016/j.xgen.2022.100215
PMID
36777188
PMCID
PMC9903705
PubMedCentral® Posted Date
11-9-2022
PubMedCentral® Full Text Version
Post-print
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.
Keywords
single-cell genomics, triple-negative breast cancer, intratumor heterogeneity, mutational evolution, breast cancer
Published Open-Access
yes
Recommended Citation
Leighton, Jake; Hu, Min; Sei, Emi; et al., "Reconstructing Mutational Lineages in Breast Cancer by Multi-Patient-Targeted Single-Cell DNA Sequencing" (2023). Faculty, Staff and Student Publications. 4881.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4881
Graphical Abstract
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