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Breast Tumors Maintain a Reservoir of Subclonal Diversity During Expansion
Our knowledge of copy number evolution during the expansion of primary breast tumors is limited(1,2). 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 triple-negative breast cancers (TNBCs)...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049101/ https://www.ncbi.nlm.nih.gov/pubmed/33762732 http://dx.doi.org/10.1038/s41586-021-03357-x |
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author | Minussi, Darlan Conterno Nicholson, Michael D. Ye, Hanghui Davis, Alexander Wang, Kaile Baker, Toby Tarabichi, Maxime Sei, Emi Du, Haowei Rabbani, Mashiat Peng, Cheng Hu, Min Bai, Shanshan Lin, Yu-wei Schalck, Aislyn Multani, Asha Ma, Jin McDonald, Thomas O. Casasent, Anna Barrera, Angelica Chen, Hui Lim, Bora Arun, Banu Meric-Bernstam, Funda Van Loo, Peter Michor, Franziska Navin, Nicholas E. |
author_facet | Minussi, Darlan Conterno Nicholson, Michael D. Ye, Hanghui Davis, Alexander Wang, Kaile Baker, Toby Tarabichi, Maxime Sei, Emi Du, Haowei Rabbani, Mashiat Peng, Cheng Hu, Min Bai, Shanshan Lin, Yu-wei Schalck, Aislyn Multani, Asha Ma, Jin McDonald, Thomas O. Casasent, Anna Barrera, Angelica Chen, Hui Lim, Bora Arun, Banu Meric-Bernstam, Funda Van Loo, Peter Michor, Franziska Navin, Nicholas E. |
author_sort | Minussi, Darlan Conterno |
collection | PubMed |
description | Our knowledge of copy number evolution during the expansion of primary breast tumors is limited(1,2). 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 triple-negative breast cancers (TNBCs) and 4 cell lines. Our data shows that breast tumors and cell lines are comprised of 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 LOH events and genome doubling, there was a period of transient genomic instability followed by ongoing copy number evolution during the primary tumor expansion. By subcloning single daughter cells in culture, we show that tumor cells re-diversify their genomes and do not retain isogenic properties. These data show that TNBCs continue to evolve chromosome aberrations and maintain a reservoir of subclonal diversity during primary tumor growth. |
format | Online Article Text |
id | pubmed-8049101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-80491012021-09-24 Breast Tumors Maintain a Reservoir of Subclonal Diversity During Expansion Minussi, Darlan Conterno Nicholson, Michael D. Ye, Hanghui Davis, Alexander Wang, Kaile Baker, Toby Tarabichi, Maxime Sei, Emi Du, Haowei Rabbani, Mashiat Peng, Cheng Hu, Min Bai, Shanshan Lin, Yu-wei Schalck, Aislyn Multani, Asha Ma, Jin McDonald, Thomas O. Casasent, Anna Barrera, Angelica Chen, Hui Lim, Bora Arun, Banu Meric-Bernstam, Funda Van Loo, Peter Michor, Franziska Navin, Nicholas E. Nature Article Our knowledge of copy number evolution during the expansion of primary breast tumors is limited(1,2). 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 triple-negative breast cancers (TNBCs) and 4 cell lines. Our data shows that breast tumors and cell lines are comprised of 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 LOH events and genome doubling, there was a period of transient genomic instability followed by ongoing copy number evolution during the primary tumor expansion. By subcloning single daughter cells in culture, we show that tumor cells re-diversify their genomes and do not retain isogenic properties. These data show that TNBCs continue to evolve chromosome aberrations and maintain a reservoir of subclonal diversity during primary tumor growth. 2021-03-24 2021-04 /pmc/articles/PMC8049101/ /pubmed/33762732 http://dx.doi.org/10.1038/s41586-021-03357-x Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Minussi, Darlan Conterno Nicholson, Michael D. Ye, Hanghui Davis, Alexander Wang, Kaile Baker, Toby Tarabichi, Maxime Sei, Emi Du, Haowei Rabbani, Mashiat Peng, Cheng Hu, Min Bai, Shanshan Lin, Yu-wei Schalck, Aislyn Multani, Asha Ma, Jin McDonald, Thomas O. Casasent, Anna Barrera, Angelica Chen, Hui Lim, Bora Arun, Banu Meric-Bernstam, Funda Van Loo, Peter Michor, Franziska Navin, Nicholas E. Breast Tumors Maintain a Reservoir of Subclonal Diversity During Expansion |
title | Breast Tumors Maintain a Reservoir of Subclonal Diversity During Expansion |
title_full | Breast Tumors Maintain a Reservoir of Subclonal Diversity During Expansion |
title_fullStr | Breast Tumors Maintain a Reservoir of Subclonal Diversity During Expansion |
title_full_unstemmed | Breast Tumors Maintain a Reservoir of Subclonal Diversity During Expansion |
title_short | Breast Tumors Maintain a Reservoir of Subclonal Diversity During Expansion |
title_sort | breast tumors maintain a reservoir of subclonal diversity during expansion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049101/ https://www.ncbi.nlm.nih.gov/pubmed/33762732 http://dx.doi.org/10.1038/s41586-021-03357-x |
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