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Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations
Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. He...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474888/ https://www.ncbi.nlm.nih.gov/pubmed/28429735 http://dx.doi.org/10.1038/ncomms14944 |
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author | Brown, David Smeets, Dominiek Székely, Borbála Larsimont, Denis Szász, A. Marcell Adnet, Pierre-Yves Rothé, Françoise Rouas, Ghizlane Nagy, Zsófia I. Faragó, Zsófia Tőkés, Anna-Mária Dank, Magdolna Szentmártoni, Gyöngyvér Udvarhelyi, Nóra Zoppoli, Gabriele Pusztai, Lajos Piccart, Martine Kulka, Janina Lambrechts, Diether Sotiriou, Christos Desmedt, Christine |
author_facet | Brown, David Smeets, Dominiek Székely, Borbála Larsimont, Denis Szász, A. Marcell Adnet, Pierre-Yves Rothé, Françoise Rouas, Ghizlane Nagy, Zsófia I. Faragó, Zsófia Tőkés, Anna-Mária Dank, Magdolna Szentmártoni, Gyöngyvér Udvarhelyi, Nóra Zoppoli, Gabriele Pusztai, Lajos Piccart, Martine Kulka, Janina Lambrechts, Diether Sotiriou, Christos Desmedt, Christine |
author_sort | Brown, David |
collection | PubMed |
description | Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common ‘metastatic precursor’. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination. |
format | Online Article Text |
id | pubmed-5474888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54748882017-07-03 Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations Brown, David Smeets, Dominiek Székely, Borbála Larsimont, Denis Szász, A. Marcell Adnet, Pierre-Yves Rothé, Françoise Rouas, Ghizlane Nagy, Zsófia I. Faragó, Zsófia Tőkés, Anna-Mária Dank, Magdolna Szentmártoni, Gyöngyvér Udvarhelyi, Nóra Zoppoli, Gabriele Pusztai, Lajos Piccart, Martine Kulka, Janina Lambrechts, Diether Sotiriou, Christos Desmedt, Christine Nat Commun Article Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common ‘metastatic precursor’. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination. Nature Publishing Group 2017-04-20 /pmc/articles/PMC5474888/ /pubmed/28429735 http://dx.doi.org/10.1038/ncomms14944 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Brown, David Smeets, Dominiek Székely, Borbála Larsimont, Denis Szász, A. Marcell Adnet, Pierre-Yves Rothé, Françoise Rouas, Ghizlane Nagy, Zsófia I. Faragó, Zsófia Tőkés, Anna-Mária Dank, Magdolna Szentmártoni, Gyöngyvér Udvarhelyi, Nóra Zoppoli, Gabriele Pusztai, Lajos Piccart, Martine Kulka, Janina Lambrechts, Diether Sotiriou, Christos Desmedt, Christine Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations |
title | Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations |
title_full | Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations |
title_fullStr | Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations |
title_full_unstemmed | Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations |
title_short | Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations |
title_sort | phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474888/ https://www.ncbi.nlm.nih.gov/pubmed/28429735 http://dx.doi.org/10.1038/ncomms14944 |
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