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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)...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
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.
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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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