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Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903705/ https://www.ncbi.nlm.nih.gov/pubmed/36777188 http://dx.doi.org/10.1016/j.xgen.2022.100215 |
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author | Leighton, Jake Hu, Min Sei, Emi Meric-Bernstam, Funda Navin, Nicholas E. |
author_facet | Leighton, Jake Hu, Min Sei, Emi Meric-Bernstam, Funda Navin, Nicholas E. |
author_sort | Leighton, Jake |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9903705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99037052023-02-10 Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing Leighton, Jake Hu, Min Sei, Emi Meric-Bernstam, Funda Navin, Nicholas E. Cell Genom Technology 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. Elsevier 2022-11-09 /pmc/articles/PMC9903705/ /pubmed/36777188 http://dx.doi.org/10.1016/j.xgen.2022.100215 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Technology Leighton, Jake Hu, Min Sei, Emi Meric-Bernstam, Funda Navin, Nicholas E. Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing |
title | Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing |
title_full | Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing |
title_fullStr | Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing |
title_full_unstemmed | Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing |
title_short | Reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell DNA sequencing |
title_sort | reconstructing mutational lineages in breast cancer by multi-patient-targeted single-cell dna sequencing |
topic | Technology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903705/ https://www.ncbi.nlm.nih.gov/pubmed/36777188 http://dx.doi.org/10.1016/j.xgen.2022.100215 |
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