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Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient
Currently, clinical characterization of metastatic breast cancer is based on tissue samples taken at time of diagnosis. However, tissue biopsies are invasive and tumors are continuously evolving, which indicates the need for minimally invasive longitudinal assessment of the tumor. Blood-based liquid...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784493/ https://www.ncbi.nlm.nih.gov/pubmed/33203646 http://dx.doi.org/10.1101/mcs.a005819 |
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author | Welter, Lisa Xu, Liya McKinley, Dillon Dago, Angel E. Prabakar, Rishvanth K. Restrepo-Vassalli, Sara Xu, Kevin Rodriguez-Lee, Mariam Kolatkar, Anand Nevarez, Rafael Ruiz, Carmen Nieva, Jorge Kuhn, Peter Hicks, James |
author_facet | Welter, Lisa Xu, Liya McKinley, Dillon Dago, Angel E. Prabakar, Rishvanth K. Restrepo-Vassalli, Sara Xu, Kevin Rodriguez-Lee, Mariam Kolatkar, Anand Nevarez, Rafael Ruiz, Carmen Nieva, Jorge Kuhn, Peter Hicks, James |
author_sort | Welter, Lisa |
collection | PubMed |
description | Currently, clinical characterization of metastatic breast cancer is based on tissue samples taken at time of diagnosis. However, tissue biopsies are invasive and tumors are continuously evolving, which indicates the need for minimally invasive longitudinal assessment of the tumor. Blood-based liquid biopsies provide minimal invasive means for serial sampling over the course of treatment and the opportunity to adjust therapies based on molecular markers. Here, we aim to identify cellular changes that occur in breast cancer over the lifespan of an affected patient through single-cell proteomic and genomic analysis of longitudinally sampled solid and liquid biopsies. Three solid and 17 liquid biopsies from peripheral blood of an ER(+)/HER2(−) metastatic breast cancer patient collected over 4 years and eight treatment regimens were analyzed for morphology, protein expression, copy-number alterations, and single-nucleotide variations. Analysis of 563 single morphometrically similar circulating tumor cells (CTCs) and 13 cell-free DNA (cfDNA) samples along with biopsies of the primary and metastatic tumor revealed progressive genomic evolution away from the primary tumor profiles, along with changes in ER expression and the appearance of resistance mutations. Both the abundance and the genomic alterations of CTCs and cfDNA were highly correlated and consistent with genomic alterations in the tissue samples. We demonstrate that genomic evolution and acquisition of drug resistance can be detected in real time and at single-cell resolution through liquid biopsy analytes and highlight the utility of liquid biopsies to guide treatment decisions. |
format | Online Article Text |
id | pubmed-7784493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77844932021-01-14 Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient Welter, Lisa Xu, Liya McKinley, Dillon Dago, Angel E. Prabakar, Rishvanth K. Restrepo-Vassalli, Sara Xu, Kevin Rodriguez-Lee, Mariam Kolatkar, Anand Nevarez, Rafael Ruiz, Carmen Nieva, Jorge Kuhn, Peter Hicks, James Cold Spring Harb Mol Case Stud Research Article Currently, clinical characterization of metastatic breast cancer is based on tissue samples taken at time of diagnosis. However, tissue biopsies are invasive and tumors are continuously evolving, which indicates the need for minimally invasive longitudinal assessment of the tumor. Blood-based liquid biopsies provide minimal invasive means for serial sampling over the course of treatment and the opportunity to adjust therapies based on molecular markers. Here, we aim to identify cellular changes that occur in breast cancer over the lifespan of an affected patient through single-cell proteomic and genomic analysis of longitudinally sampled solid and liquid biopsies. Three solid and 17 liquid biopsies from peripheral blood of an ER(+)/HER2(−) metastatic breast cancer patient collected over 4 years and eight treatment regimens were analyzed for morphology, protein expression, copy-number alterations, and single-nucleotide variations. Analysis of 563 single morphometrically similar circulating tumor cells (CTCs) and 13 cell-free DNA (cfDNA) samples along with biopsies of the primary and metastatic tumor revealed progressive genomic evolution away from the primary tumor profiles, along with changes in ER expression and the appearance of resistance mutations. Both the abundance and the genomic alterations of CTCs and cfDNA were highly correlated and consistent with genomic alterations in the tissue samples. We demonstrate that genomic evolution and acquisition of drug resistance can be detected in real time and at single-cell resolution through liquid biopsy analytes and highlight the utility of liquid biopsies to guide treatment decisions. Cold Spring Harbor Laboratory Press 2020-12 /pmc/articles/PMC7784493/ /pubmed/33203646 http://dx.doi.org/10.1101/mcs.a005819 Text en © 2020 Welter et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
spellingShingle | Research Article Welter, Lisa Xu, Liya McKinley, Dillon Dago, Angel E. Prabakar, Rishvanth K. Restrepo-Vassalli, Sara Xu, Kevin Rodriguez-Lee, Mariam Kolatkar, Anand Nevarez, Rafael Ruiz, Carmen Nieva, Jorge Kuhn, Peter Hicks, James Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient |
title | Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient |
title_full | Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient |
title_fullStr | Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient |
title_full_unstemmed | Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient |
title_short | Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient |
title_sort | treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784493/ https://www.ncbi.nlm.nih.gov/pubmed/33203646 http://dx.doi.org/10.1101/mcs.a005819 |
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